The renal excretion of gentamicin, an aminoglycoside antibiotic, was studied in the isolated perfused rat kidney (IPRK) model. Dose-linearity experiments were carried out at four doses (400, 800, 1600, 3200 μg), targ...The renal excretion of gentamicin, an aminoglycoside antibiotic, was studied in the isolated perfused rat kidney (IPRK) model. Dose-linearity experiments were carried out at four doses (400, 800, 1600, 3200 μg), targeting initial perfusate levels of 5, 10, 20 and 40 μg/ml. Additionally, gentamicin was co-perfused with sodium bicarbonate (0.25 mM) and/or cimetidine (2 mM) to evaluate the effect of urinary alkalization and secretory inhibition on gentamicin excretion and kidney accumulation. Gentamicin displayed net reabsorption in the IPRK, consistent with extensive luminal uptake. Kinetic analysis indicated that luminal transport of gentamicin (kidney ? urine) is the rate-determining step for gentamicin urinary excretion. Clearance and cumulative excretion decreased with increased gentamicin dose. Gentamicin kidney accumulation, estimated by mass balance, ranged from ~20% - 30%. Urinary alkalization significantly increased gentamicin excretion, with no effect on kidney accumulation. Conversely, cimetidine co-administration did not affect gentamicin clearance in the IPRK, but kidney accumulation was significantly reduced. When both sodium bicarbonate and cimetidine were administered together, gentamicin kidney accumulation decreased ~80% with corresponding increases in clearance and excretion ratio (XR) compared to gentamicin alone. A main strategy to reduce the incidence of nephrotoxicity with gentamicin therapy (up to ~25%) involves reducing kidney accumulation of the compound. The results of this research suggest that the combination of urinary alkalization and inhibition of basolateral secretion (blood → kidney) may be a viable approach to mitigate aminoglycoside toxicity, and warrants further investigation.展开更多
BACKGROUND: Ligustrazine (tetramethylpyrazine) decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE: To explore t...BACKGROUND: Ligustrazine (tetramethylpyrazine) decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE: To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING: The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS: Ligustrazine parenteral solution (Qiqihar Pharmaceutical Factory, China) and gentamicin sulfate (Shenyang First Pharmaceutical Factory, China) were used in this experiment.METHODS: White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection + saline, gentamicin sulfate injection + ligustrazine, and ligustrazine + saline, respectively.MAIN OUTCOME MEASURES: Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS: Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 (P〉0.05). Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION: Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.展开更多
In order to clarify whether gentamicin (GM) could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg...In order to clarify whether gentamicin (GM) could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg·kg<sup>-10</sup>·d<sup>-1</sup> GM for 3 consecutive days.The animals ofthe control group received equal amount of normal saline.It was found that some myelin figuresappeared in the epithelial cells of the proximal tubules as early as 1 h after a single GM injec-tion;severe swelling,degeneration,and obvious changes of the organelles were seen in the en-dothelial cells of the glomerular capillaries,the podocytes and the epithelial cells of the proxi-mal tubules 24 h after an injection of GM;and fusion of the processes of podocytes,thickeningof the glomerular membrane and necrosis of the epithelial cells of a part of the’proximal tubuleswere encountered 24h after the 3rd GM injection.These findings demonstrate that GM can in-jure not only the proximal tubules but also the glomeruli in rabbits.展开更多
To gain insights into the ototoxic effects of aminoglycoside antibiotics(AmAn) and delayed peripheral ganglion neuron death in the inner ear.experimental animal models were widely used with several different approache...To gain insights into the ototoxic effects of aminoglycoside antibiotics(AmAn) and delayed peripheral ganglion neuron death in the inner ear.experimental animal models were widely used with several different approaches including AmAn systemic injections,combination treatment of AmAn and diuretics,or local application of AmAn.In these approaches,systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear.Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells,but it is impossible to damage the vestibular system.Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear.Therefore,AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death.In current studies,guinea pigs were unilaterally treated with a high concentration of gentamicin(GM,40 nig/ml) through the tympanic membrane into the middle ear cavity.Auditory functions and vestibular functions were measured before and after GM treatment.The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment.The results showed that both auditory and vestibular functions were completely abolished after GM treatment.The sensory hair cells were totally missing in the cochlea,and severely destroyed in vestibular end-organs.The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%.However,no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment.These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration.This model might be useful for studies of hair cell regenerations,delayed degeneration of peripheral auditory neurons,and/or vestibular compensation.In addition,a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.展开更多
Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were d...Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.展开更多
Objective:To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4000(PEG-4000) for oral administration.Methods:Gentamicin lipospheres were prepared by melt-emulsification us...Objective:To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4000(PEG-4000) for oral administration.Methods:Gentamicin lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon(?) 90H in Beeswax as the lipid matrix containing PEC-4000.These lipospheres were characterized by evaluating on encapsulation efficiency,loading capacity,change in pH and the release profile. Antimicrobial activities were evaluated against Escherichia coli,Pseudomonas aeruginosa. Salmonella paratyphii and Staphylococcus aureus using the agar diffusion method.Results: Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month.The release of gentamicin in vitro varied widely with the PEC-4000 contents. Moreover,significant(P>0.05) amount of gentamicin was released in vivo from the formulation. The encapsulation and loading capacity were all high,indicating the ability of the lipids to take up the drug.The antimicrobial activities were very high especially against Pseudomonas compare to other test organisms.This strongly suggested that the formulation retain its bioactive characteristics.Conclusions:This study strongly suggest that the issue of gentamicin stability and poor absorption in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.展开更多
A systematic approach was developed to investigate the stability of gentamicin sulfate(GS) and GS/poly(lacticco-glycolic acid)(PLGA) coatings on hydroxyapatite surfaces.The influence of environmental factors(light,hum...A systematic approach was developed to investigate the stability of gentamicin sulfate(GS) and GS/poly(lacticco-glycolic acid)(PLGA) coatings on hydroxyapatite surfaces.The influence of environmental factors(light,humidity,oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry.GS coated rods were found to be stable across the range of environments assessed,with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition.In contrast,rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C,75% relative humidity or exposure to light.The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect.Finally,liquid chromatography–mass spectrometry analysis revealed that known gentamines C_1,C_1 aand C_2were the major degradants formed.Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.展开更多
Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg...Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg/d for 10 d),Heracleum persicum(750 mg/kg/d),and gentamicin(10 d)+Heracleum persicum extract at three different doses(250,500,and 750 mg/kg/d for 40 d).Urine creatinine,urea,protein,and albumin levels were determined.In addition,serum urea,creatinine,sodium,potassium,cytokines(TNF-α,IL-1β,IL-6,and IL-10),glutathione peroxidase activity,total antioxidant capacity,kidney malondialdehyde,stereological parameters,and expressions of apoptosis-related genes(p53,Bax,Bcl-2,and caspase-3)were measured.The LD50 of Heracleum persicum extract was determined based on Lorke’s method.Histopathological evaluation was also performed.Results:In addition to decreased urine protein and albumin,and increased creatinine and urea,co-treatment with gentamicin and Heracleum persicum significantly reduced levels of creatinine and urea,and increased sodium and potassium in serum.Heracleum persicum treatment also improved stereological parameters and serum inflammatory cytokines.There was a significant increase in serum glutathione peroxidase activity and total antioxidant capacity as well as a reduction in malondialdehyde level.Furthermore,treatment with Heracleum persicum extracts downregulated p53,caspase-3,and Bax and upregulated Bcl-2 expressions.In histopathological evaluation,Heracleum persicum extracts showed protection against gentamicin-induced renal damages.Conclusions:Heracleum persicum exhibits protective effects against gentamicin-induced structural and functional renal impairments.展开更多
Objective To study gentamicin injury mechanisms using postnatal mouse cochlear spiral gangcells (SGC). Methods SGCs were isolated using a combinatorial approach of enzymatic digestion and mechanical separation from ...Objective To study gentamicin injury mechanisms using postnatal mouse cochlear spiral gangcells (SGC). Methods SGCs were isolated using a combinatorial approach of enzymatic digestion and mechanical separation from P2 - 6 Kunming mouse cochleae. After 4 days, cultured SGCs were fixed with 4% paraformaldehyde at room temperature for immunocytochemical examination using the methods of S-P and the monoclonal antibody against mouse neurofilament protein (Neurofilament-68/200Kda, NF-L+ H). SGCs were randomly divided into a blank control group and three gentamicin treatment groups (medium gentamicin concentration at 50 mg/L, 100 mg/L and 150 mg/L respectively), SGCs were collected and examined under a transmission electron microscope after being cultured for 48 h. Results SGC primary culture was successful. SGC cytoplasm and neurites were dyed brownish yellow by the monoelonal mouse neurofilament protein antibody. SGCs showed classical bipolar neuron appearance. Under the transmission electron microscope,.gentamicin treated SGCs showed morphological features different compared to those in the blank control group, which might indicate apoptosis. Conclusion Our results indicate that gentamicin has direct toxic effects on cochlear SGCs in mice and the injury mechanism is closely related with apoptosis. Damage to mitochor, dria may play an important role in the process.展开更多
Objective To investigate the early change of cochlear ribbon synapses on inner hair cells in response to aminoglycoside ototoxicity. Methods C57BL/6J mice received intraperitoneal injection of gentamicin (100 mg/kg/da...Objective To investigate the early change of cochlear ribbon synapses on inner hair cells in response to aminoglycoside ototoxicity. Methods C57BL/6J mice received intraperitoneal injection of gentamicin (100 mg/kg/day), and the apical coil organ of Corti was examined on the 4th, 7th and 10th day (n=10). Litter-mates without gentamicin treatment served as controls (n=10). RIBEYE on the presynaptic membrane and AMPA receptors on the postsynaptic membrane were labeled with CtBP2 or GluR2/3 respectively. Three di-mension reconstruction was conducted using the 3DS MAX 8.0 software. Results There were no disruptions of outer or inner hair cells in all groups. However, the number of ribbon synapses on cochlear inner hair cells increased significantly within 7 days after gentamicin exposure (P<0.01), followed by a significant de-crease after 7 days.Conclusion During the early stage of aminoglycoside ototoxicity, increased population of cochlear ribbon synapses may indicate a significant down-regulation of synaptic function.展开更多
In this work bactericidal study of silver nanoparticles was taken up in combination with two standard antibiotics, ampicillin and gentamycin, for Salmonella Typhi. The antibacterial activities of antibiotics were incr...In this work bactericidal study of silver nanoparticles was taken up in combination with two standard antibiotics, ampicillin and gentamycin, for Salmonella Typhi. The antibacterial activities of antibiotics were increased in the presence of AgNPs against test strains. The higher enhancing effect was observed for ampicillin in comparison to gentamicin against test strains. Silver nanoparticles were synthesized elctrolytically using silver wire of 99% purity as anode and carbon rod wrapped with LDPE as cathode. Silver nitrate [of Merck] of 0.01N is used as an electrolyte. Here tea extract is added as capping and mild reducing agent. The polyphenols theaflavins and thearubigins, present in tea perform the role of stabilizing or capping agents due to their bulky and steric nature. A brown coloured colloidal solution of silver nanoparticles is obtained. The as-synthesized silver nanoparticles were characterized using XRD, TEM and UV-Vis spectroscopy.展开更多
BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in c...BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in children.CASE SUMMARY We report the case of a 1-year-old girl with a choroid plexus papilloma, who developed postoperative nosocomial meningitis due to MDRAB. The bacterial strain was sensitive only to tigecycline and colistin, and showed varying degrees of resistance to penicillin, amikacin, ceftriaxone, cefixime, cefotaxime,ciprofloxacin, levofloxacin, gentamicin, meropenem, imipenem, and tobramycin.She was cured with intravenous doxycycline and intraventricular gentamicin treatment.CONCLUSION Doxycycline and gentamicin were shown to be effective and safe in the treatment of a pediatric case of MDRAB meningitis.展开更多
Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute...Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5(KM) mg ethyl acetate floral extract/kg hodv weight was administered to albino rats(five females,five males).Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD<sub>50</sub>】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels(P】0.01).Conclusions: The present study indicates a verv important role of reactive oxygen species(BOS) and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.展开更多
Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin...Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.展开更多
BACKGROUND: It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary...BACKGROUND: It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE: To explore morphological changes of choline acetyltransferase (ChAT)-positive neurons in the paraolivary nucleus (PON) of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING: Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS: A total of 48 healthy guinea pigs were randomly divided into model (n = 40) and control (n = 8) groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS: Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES: Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS: ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration (P 〈 0.05). In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection (P 〈 0.05), whereas cell number significantly decreased at ;three weeks after injection (P 〈 0.05). Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration (P 〈 0.05). CONCLUSION: Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.展开更多
Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentami...Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentamicin,and Allolobophora caliginosa coelomic fluid-treated groups.Toxicity was established after injection of gentamicin daily for 8 days at a dose of 100 mg/kg.Aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,total proteins,albumin,creatinine,urea,uric acid,malondialdehyde,glutathione,catalase and histopathology of tissues were investigated in the study.Results:Allolobophora caliginosa coelomic fluid significantly decreased urea,creatinine,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and malondialdehyde levels while significantly increasing levels of total proteins,albumin,glutathione and catalase.The histopathological investigation showed partial restoration of renal and hepatic architecture.Conclusions:This study shows the potency of Allolobophora caliginosa coelomic fluid in improving the biochemical and histopathological changes induced by gentamicin in the liver and kidney of the rats.展开更多
Objective: To evaluate the toxic potential of Launaea taraxacifolia leaf extract(LTE) in rats within 14 d of oral administration and also assess the potential of LTE in protecting against kidney injury induced by gent...Objective: To evaluate the toxic potential of Launaea taraxacifolia leaf extract(LTE) in rats within 14 d of oral administration and also assess the potential of LTE in protecting against kidney injury induced by gentamicin using rat model.Methods: The protective ability of LTE was done after sub-acute toxicity evaluation has been carried out. Acute Kidney Injury(AKI) was induced by gentamicin at a dose of 160 mg/kg intraperitoneal i.p. Parameters and indicators considered include mortality,clinical signs, body and organ weights, haematological and clinical chemistry parameters.Gross examination and histopathological assessment was also done on selected internal organs.Results: There were no treatment-related deaths or changes in clinical signs, haematological and clinical chemistry indices during sub-acute toxicity studies with the exception of creatinine levels. This was confirmed by micrographs obtained from histopathological analysis. Co-administration of LTE with 160 mg/kg of gentamicin(i.p) markedly decreased the levels of urea and creatinine when compared to negative control group.Histological studies of kidney tissues showed an insignificant change in tubular epithelium in LTE plus gentamicin treated group compared to LTE treated only.Conclusions: Data obtained show that ethanolic leaf extract of Launaea taraxacifolia is non-toxic within a 14 d administration at a maximum dose of 1 000 mg/kg bwt and also possesses the ability to protect against gentamicin-induced kidney damage in rats at a dose of 300 mg/kg bwt.展开更多
文摘The renal excretion of gentamicin, an aminoglycoside antibiotic, was studied in the isolated perfused rat kidney (IPRK) model. Dose-linearity experiments were carried out at four doses (400, 800, 1600, 3200 μg), targeting initial perfusate levels of 5, 10, 20 and 40 μg/ml. Additionally, gentamicin was co-perfused with sodium bicarbonate (0.25 mM) and/or cimetidine (2 mM) to evaluate the effect of urinary alkalization and secretory inhibition on gentamicin excretion and kidney accumulation. Gentamicin displayed net reabsorption in the IPRK, consistent with extensive luminal uptake. Kinetic analysis indicated that luminal transport of gentamicin (kidney ? urine) is the rate-determining step for gentamicin urinary excretion. Clearance and cumulative excretion decreased with increased gentamicin dose. Gentamicin kidney accumulation, estimated by mass balance, ranged from ~20% - 30%. Urinary alkalization significantly increased gentamicin excretion, with no effect on kidney accumulation. Conversely, cimetidine co-administration did not affect gentamicin clearance in the IPRK, but kidney accumulation was significantly reduced. When both sodium bicarbonate and cimetidine were administered together, gentamicin kidney accumulation decreased ~80% with corresponding increases in clearance and excretion ratio (XR) compared to gentamicin alone. A main strategy to reduce the incidence of nephrotoxicity with gentamicin therapy (up to ~25%) involves reducing kidney accumulation of the compound. The results of this research suggest that the combination of urinary alkalization and inhibition of basolateral secretion (blood → kidney) may be a viable approach to mitigate aminoglycoside toxicity, and warrants further investigation.
基金the National Natural Science Foundation of China,No. 30672739the Scientific Research Program of Education Department of Liaoning Province,No. 2008722the Science and Technology Foundation of Liaoning Province,No. 20031032
文摘BACKGROUND: Ligustrazine (tetramethylpyrazine) decreases ototoxicity induced by gentamicin and facilitates hair cell regeneration and repair, but the precise mechanisms remain controversial.OBJECTIVE: To explore the protective effects of ligustrazine on gentamicin ototoxicity by determining heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis of guinea pigs at different time points.DESIGN, TIME AND SETTING: The randomized, controlled study was performed at the Laboratory of Physiology, Shenyang Medical College of China in 2007.MATERIALS: Ligustrazine parenteral solution (Qiqihar Pharmaceutical Factory, China) and gentamicin sulfate (Shenyang First Pharmaceutical Factory, China) were used in this experiment.METHODS: White guinea pigs with red eyes were randomly intraperitoneally administered gentamicin sulfate injection + saline, gentamicin sulfate injection + ligustrazine, and ligustrazine + saline, respectively.MAIN OUTCOME MEASURES: Auditory brains tern response threshold was measured. Immunohistochemistry, in situ hybridization, and image analyzing techniques were utilized to determine heat shock protein 70 mRNA and protein expression in cochlear stria vascularis of guinea pigs.RESULTS: Following gentamicin ototoxicity, the auditory brainstem response threshold increased, peaked on day 3, and then decreased with increased time after drug withdrawal. The auditory brainstem response threshold was significantly diminished following ligustrazine intervention, but recovered to normal on day 30 (P〉0.05). Heat shock protein 70 expression also increased, peaked on day 3, and then decreased in the cochlear stria vascularis of guinea pigs following gentamicin ototoxicity. Ligustrazine intervention resulted in decreased heat shock protein 70 expression in the cochlear stria vascularis, which recovered to normal on day 14. Heat shock protein 70 mRNA expression increased in the cochlear stria vascularis following gentamicin ototoxicity, but ligustrazine intervention resulted in decreased levels. CONCLUSION: Ligustrazine significantly ameliorated gentamicin ototoxicity by reducing heat shock protein 70 mRNA and protein expression in the cochlear stria vascularis.
文摘In order to clarify whether gentamicin (GM) could damage the renal glomeruli,theultrastructural changes of the renal cortex were observed in rabbits after they received a singleinjection of 100 mg/kg GM or 100 mg·kg<sup>-10</sup>·d<sup>-1</sup> GM for 3 consecutive days.The animals ofthe control group received equal amount of normal saline.It was found that some myelin figuresappeared in the epithelial cells of the proximal tubules as early as 1 h after a single GM injec-tion;severe swelling,degeneration,and obvious changes of the organelles were seen in the en-dothelial cells of the glomerular capillaries,the podocytes and the epithelial cells of the proxi-mal tubules 24 h after an injection of GM;and fusion of the processes of podocytes,thickeningof the glomerular membrane and necrosis of the epithelial cells of a part of the’proximal tubuleswere encountered 24h after the 3rd GM injection.These findings demonstrate that GM can in-jure not only the proximal tubules but also the glomeruli in rabbits.
基金supported by the National Nature Science Foundation of China(No.81170912)the Major State Basic Research Development Program of China(973 Program,No.2014CB943003)
文摘To gain insights into the ototoxic effects of aminoglycoside antibiotics(AmAn) and delayed peripheral ganglion neuron death in the inner ear.experimental animal models were widely used with several different approaches including AmAn systemic injections,combination treatment of AmAn and diuretics,or local application of AmAn.In these approaches,systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear.Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells,but it is impossible to damage the vestibular system.Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear.Therefore,AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death.In current studies,guinea pigs were unilaterally treated with a high concentration of gentamicin(GM,40 nig/ml) through the tympanic membrane into the middle ear cavity.Auditory functions and vestibular functions were measured before and after GM treatment.The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment.The results showed that both auditory and vestibular functions were completely abolished after GM treatment.The sensory hair cells were totally missing in the cochlea,and severely destroyed in vestibular end-organs.The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%.However,no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment.These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration.This model might be useful for studies of hair cell regenerations,delayed degeneration of peripheral auditory neurons,and/or vestibular compensation.In addition,a potential problem of ABR recording for unilateral deafness and issues about vestibular compensation are also discussed.
文摘Objective:To evaluate nephroprotective potential of Solarium xanthocarpum(S.xanthocarpum) fruit extract(SXE) against gentamicin(GM) induced nephrotoxicity) and renal dysfunction. Methods:Twenty-four Wistar rats were divided into four groups(n=6).Control rats that received normal saline(i.p.) and 0.5%carboxymethyl cellulose(p.o.) per day lor 8 d.Nephrotoxicity was induced in rats by intraperitoneal administration of GM(100 mg/kg/d for 8 d) and were treated with SXE(200 and 400 mg/kg/d(p.o.) for 8 d).Plasma and urine urea and creatinine,kidney weight,urine output,blood urea nitrogen,renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats.Results:It was observed that the GM treatment induced significant elevation(P【0.001) in plasma and urine urea,creatinine,kidney weight,blood urea nitrogen, renal lipid peroxidation along with significant decrement(P【0.001) in urine output,renal enzymatic and non-enzymatic antioxidants.SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement(up to P【0.001) in plasma and mine urea and creatinine, renal lipid peroxidation along with significanl increment(up to P【0.001) in renal enzymatic and non-enzvmatic antioxidants.Histological obsenatioiis of kidney tissues too correlated with the biochemical obsenatioiis.Conclusions:These finding powerfully supports that S,xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its elhnomedicinal use.
文摘Objective:To formulate gentamicin liposphere by solvent-melting method using lipids and polyethylene glycol 4000(PEG-4000) for oral administration.Methods:Gentamicin lipospheres were prepared by melt-emulsification using 30%w/w Phospholipon(?) 90H in Beeswax as the lipid matrix containing PEC-4000.These lipospheres were characterized by evaluating on encapsulation efficiency,loading capacity,change in pH and the release profile. Antimicrobial activities were evaluated against Escherichia coli,Pseudomonas aeruginosa. Salmonella paratyphii and Staphylococcus aureus using the agar diffusion method.Results: Photomicrographs revealed spherical particles within a micrometer range with minimal growth after 1 month.The release of gentamicin in vitro varied widely with the PEC-4000 contents. Moreover,significant(P>0.05) amount of gentamicin was released in vivo from the formulation. The encapsulation and loading capacity were all high,indicating the ability of the lipids to take up the drug.The antimicrobial activities were very high especially against Pseudomonas compare to other test organisms.This strongly suggested that the formulation retain its bioactive characteristics.Conclusions:This study strongly suggest that the issue of gentamicin stability and poor absorption in oral formulation could be adequately addressed by tactical engineering of lipid drug delivery systems such as lipospheres.
基金jointly funded by De Puy Synthes and Enterprise Ireland IP 2010-0068
文摘A systematic approach was developed to investigate the stability of gentamicin sulfate(GS) and GS/poly(lacticco-glycolic acid)(PLGA) coatings on hydroxyapatite surfaces.The influence of environmental factors(light,humidity,oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry.GS coated rods were found to be stable across the range of environments assessed,with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition.In contrast,rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C,75% relative humidity or exposure to light.The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect.Finally,liquid chromatography–mass spectrometry analysis revealed that known gentamines C_1,C_1 aand C_2were the major degradants formed.Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.
基金financially supported by Kermanshah University of Medical Science(grant number 981004)
文摘Objective:To evaluate the effect of Heracleum persicum L.against gentamicin-induced nephrotoxicity in rats.Methods:Thirty-six Wistar rats were divided into 6 groups including control(normal saline),gentamicin(80 mg/kg/d for 10 d),Heracleum persicum(750 mg/kg/d),and gentamicin(10 d)+Heracleum persicum extract at three different doses(250,500,and 750 mg/kg/d for 40 d).Urine creatinine,urea,protein,and albumin levels were determined.In addition,serum urea,creatinine,sodium,potassium,cytokines(TNF-α,IL-1β,IL-6,and IL-10),glutathione peroxidase activity,total antioxidant capacity,kidney malondialdehyde,stereological parameters,and expressions of apoptosis-related genes(p53,Bax,Bcl-2,and caspase-3)were measured.The LD50 of Heracleum persicum extract was determined based on Lorke’s method.Histopathological evaluation was also performed.Results:In addition to decreased urine protein and albumin,and increased creatinine and urea,co-treatment with gentamicin and Heracleum persicum significantly reduced levels of creatinine and urea,and increased sodium and potassium in serum.Heracleum persicum treatment also improved stereological parameters and serum inflammatory cytokines.There was a significant increase in serum glutathione peroxidase activity and total antioxidant capacity as well as a reduction in malondialdehyde level.Furthermore,treatment with Heracleum persicum extracts downregulated p53,caspase-3,and Bax and upregulated Bcl-2 expressions.In histopathological evaluation,Heracleum persicum extracts showed protection against gentamicin-induced renal damages.Conclusions:Heracleum persicum exhibits protective effects against gentamicin-induced structural and functional renal impairments.
文摘Objective To study gentamicin injury mechanisms using postnatal mouse cochlear spiral gangcells (SGC). Methods SGCs were isolated using a combinatorial approach of enzymatic digestion and mechanical separation from P2 - 6 Kunming mouse cochleae. After 4 days, cultured SGCs were fixed with 4% paraformaldehyde at room temperature for immunocytochemical examination using the methods of S-P and the monoclonal antibody against mouse neurofilament protein (Neurofilament-68/200Kda, NF-L+ H). SGCs were randomly divided into a blank control group and three gentamicin treatment groups (medium gentamicin concentration at 50 mg/L, 100 mg/L and 150 mg/L respectively), SGCs were collected and examined under a transmission electron microscope after being cultured for 48 h. Results SGC primary culture was successful. SGC cytoplasm and neurites were dyed brownish yellow by the monoelonal mouse neurofilament protein antibody. SGCs showed classical bipolar neuron appearance. Under the transmission electron microscope,.gentamicin treated SGCs showed morphological features different compared to those in the blank control group, which might indicate apoptosis. Conclusion Our results indicate that gentamicin has direct toxic effects on cochlear SGCs in mice and the injury mechanism is closely related with apoptosis. Damage to mitochor, dria may play an important role in the process.
基金supported by grants from the National Basic Research Program of China(973Program)Beijing Natural Science Foundation(5122040)+2 种基金supported by grants from the China Postdoctoral Science Foundation(20100377920100470103)the National Natural Science Foundation of China(NSFC)(31040038)
文摘Objective To investigate the early change of cochlear ribbon synapses on inner hair cells in response to aminoglycoside ototoxicity. Methods C57BL/6J mice received intraperitoneal injection of gentamicin (100 mg/kg/day), and the apical coil organ of Corti was examined on the 4th, 7th and 10th day (n=10). Litter-mates without gentamicin treatment served as controls (n=10). RIBEYE on the presynaptic membrane and AMPA receptors on the postsynaptic membrane were labeled with CtBP2 or GluR2/3 respectively. Three di-mension reconstruction was conducted using the 3DS MAX 8.0 software. Results There were no disruptions of outer or inner hair cells in all groups. However, the number of ribbon synapses on cochlear inner hair cells increased significantly within 7 days after gentamicin exposure (P<0.01), followed by a significant de-crease after 7 days.Conclusion During the early stage of aminoglycoside ototoxicity, increased population of cochlear ribbon synapses may indicate a significant down-regulation of synaptic function.
文摘In this work bactericidal study of silver nanoparticles was taken up in combination with two standard antibiotics, ampicillin and gentamycin, for Salmonella Typhi. The antibacterial activities of antibiotics were increased in the presence of AgNPs against test strains. The higher enhancing effect was observed for ampicillin in comparison to gentamicin against test strains. Silver nanoparticles were synthesized elctrolytically using silver wire of 99% purity as anode and carbon rod wrapped with LDPE as cathode. Silver nitrate [of Merck] of 0.01N is used as an electrolyte. Here tea extract is added as capping and mild reducing agent. The polyphenols theaflavins and thearubigins, present in tea perform the role of stabilizing or capping agents due to their bulky and steric nature. A brown coloured colloidal solution of silver nanoparticles is obtained. The as-synthesized silver nanoparticles were characterized using XRD, TEM and UV-Vis spectroscopy.
基金Supported by The Shanghai Pujiang Program,No.12PJ1401500
文摘BACKGROUND Multidrug-resistant Acinetobacter baumannii(MDRAB) has emerged as an increasingly important pathogen that causes nosocomial meningitis. However,MDRAB-associated nosocomial meningitis is rarely reported in children.CASE SUMMARY We report the case of a 1-year-old girl with a choroid plexus papilloma, who developed postoperative nosocomial meningitis due to MDRAB. The bacterial strain was sensitive only to tigecycline and colistin, and showed varying degrees of resistance to penicillin, amikacin, ceftriaxone, cefixime, cefotaxime,ciprofloxacin, levofloxacin, gentamicin, meropenem, imipenem, and tobramycin.She was cured with intravenous doxycycline and intraventricular gentamicin treatment.CONCLUSION Doxycycline and gentamicin were shown to be effective and safe in the treatment of a pediatric case of MDRAB meningitis.
基金supported by Chairman,Mother Mary education Society,Vikas nagar,Hyderabad,Andhra Pradesh,India
文摘Objective:To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecomu stans for its protective effects on genlamicin-induced nephrotoxicity in albino rats. Methods:For studying acute toxicity study,single oral dose of 5(KM) mg ethyl acetate floral extract/kg hodv weight was administered to albino rats(five females,five males).Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days.Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100.200 and 300 mg/kg/day given by oral mute was determined using serum creatinine,serum uric acid,blood urea nitrogen and serum urea as indicators of kidney damage.The study groups contained six rats in each group.As nephrotoxicity of gentamicin is known to involve induction of oxidative stress,in vitro antioxidant aclivity and free radical-scavenging activity of this extract was also evaluated.Results:For acute toxicity testing both female and male rats administered with the extract at a dose of 5 000 mg/kg.The results showed no toxicity in terms of general behavior change,mortality,or change in gross appearance of internal organs(LD<sub>50</sub>】5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes.Gentamicin-induced glomerular congestion,peritubular and blood vessel congestion,epithelial desquamation,accumulation ol inflamnialoiy cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma starts along with gentamicin in a dose dependent manner.The floral extract also reduced the gentamicin-induced increase in serum creatinine,serum uric acid,blood urea nitrogen and serum urea levels(P】0.01).Conclusions: The present study indicates a verv important role of reactive oxygen species(BOS) and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.
文摘Objective:To investigate the antioxidant ef ect of an orally administered ethanol extract of nettle(Urtica dioica) and its protective role in preventing or ameliorating oxidative stress as a major factor in gentamicin-induced nephrotoxicity in male rabbits. Methods: Twenty rabbits were divided into 4 equal groups:(G1) control group,(G2) gentamicin treated group(100 mg/kg),(G3) nettle treated group(100 mg/kg),(G4) combination treated group with both gentamicin(100 mg/kg) and nettle(100 mg/kg) for 10 days. The antioxidant properties of nettle were evaluated using dif erent antioxidant tests, such as determination of glutathione and malondialdehyde levels and total phenolic content analysis. Results: Biochemical and histopathological study revealed that gentamicin caused nephrotoxicity observed clearly in the histopathological section of the kidney in the gentamicin treated group. Serum creatinine and blood urea nitrogen were biochemical indicators for nephrotoxicity which increased signii cantly in gentamicin treated group; other groups have no signii cant change in these two parameters. Nettle extract protected the rabbits from alteration in the level of blood urea nitrogen and serum creatinine when given after inducing of gentamicin nephrotoxicity. The nettle treated group showed a great ef ect as an antioxidant factor by increasing the glutathione level and reducing malondialdehyde level. No signii cant changes in biochemical parameters and no renal histopathological changes observed in the groups treated with nettle extract, which meant nettle had powerful antioxidant activity. Conclusions: Therefore, it can be assumed that the nephroprotective ef ect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.
文摘BACKGROUND: It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE: To explore morphological changes of choline acetyltransferase (ChAT)-positive neurons in the paraolivary nucleus (PON) of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING: Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS: A total of 48 healthy guinea pigs were randomly divided into model (n = 40) and control (n = 8) groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS: Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES: Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS: ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration (P 〈 0.05). In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection (P 〈 0.05), whereas cell number significantly decreased at ;three weeks after injection (P 〈 0.05). Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration (P 〈 0.05). CONCLUSION: Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.
基金supported by the Deanship of Scientific Research at King Khalid University through Research Group Project under grant number(R.G.P.1–56–40)
文摘Objective:To explore the efficacy of earthworm’s coelomic fluid against gentamicin-induced hepatic and renal toxicity in rats.Methods:The animals were divided randomly into three groups(n=6 per group):control,gentamicin,and Allolobophora caliginosa coelomic fluid-treated groups.Toxicity was established after injection of gentamicin daily for 8 days at a dose of 100 mg/kg.Aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,total proteins,albumin,creatinine,urea,uric acid,malondialdehyde,glutathione,catalase and histopathology of tissues were investigated in the study.Results:Allolobophora caliginosa coelomic fluid significantly decreased urea,creatinine,uric acid,alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and malondialdehyde levels while significantly increasing levels of total proteins,albumin,glutathione and catalase.The histopathological investigation showed partial restoration of renal and hepatic architecture.Conclusions:This study shows the potency of Allolobophora caliginosa coelomic fluid in improving the biochemical and histopathological changes induced by gentamicin in the liver and kidney of the rats.
文摘Objective: To evaluate the toxic potential of Launaea taraxacifolia leaf extract(LTE) in rats within 14 d of oral administration and also assess the potential of LTE in protecting against kidney injury induced by gentamicin using rat model.Methods: The protective ability of LTE was done after sub-acute toxicity evaluation has been carried out. Acute Kidney Injury(AKI) was induced by gentamicin at a dose of 160 mg/kg intraperitoneal i.p. Parameters and indicators considered include mortality,clinical signs, body and organ weights, haematological and clinical chemistry parameters.Gross examination and histopathological assessment was also done on selected internal organs.Results: There were no treatment-related deaths or changes in clinical signs, haematological and clinical chemistry indices during sub-acute toxicity studies with the exception of creatinine levels. This was confirmed by micrographs obtained from histopathological analysis. Co-administration of LTE with 160 mg/kg of gentamicin(i.p) markedly decreased the levels of urea and creatinine when compared to negative control group.Histological studies of kidney tissues showed an insignificant change in tubular epithelium in LTE plus gentamicin treated group compared to LTE treated only.Conclusions: Data obtained show that ethanolic leaf extract of Launaea taraxacifolia is non-toxic within a 14 d administration at a maximum dose of 1 000 mg/kg bwt and also possesses the ability to protect against gentamicin-induced kidney damage in rats at a dose of 300 mg/kg bwt.