Melatonin alleviates oxidative stress,inflammation,apoptosis,and DNA damage in acrylamide-induced nephrotoxicity in rats

Objective:To investigate the effects of melatonin on renal inflammation,oxidative stress,apoptosis,as well as DNA and tissue damage in acrylamide-induced nephrotoxicity in rats.Methods:Fifty male rats were randomly divided into five groups.The control group received distilled water by gastric lavage for 11days and the acrylamide group was administered acrylamide(50 mg/kg,i.g.)for 11 days.The MEL10+ACR and MEL20+ACR groups received intraperitoneal melatonin 10 and 20 mg/kg,respectively,for 11 days,and acrylamide(50 mg/kg,i.g.)was administered 1h after melatonin injection.The MEL20 group was injected with melatonin(20 mg/kg)for 11 days.Kidney function tests were performed and biochemical and inflammatory parameters were determined.In addition,histopathological,immunohistochemical,and immunofluorescence examinations were carried out.Results:Melatonin significantly abated acrylamide-induced rise in serum urea and creatinine levels.Acrylamide caused oxidative stress,inflammation,apoptosis,as well as DNA and tissue damage in the kidneys.Melatonin treatment alleviated acrylamide-induced renal damage by exhibiting antioxidant,anti-inflammatory,and antiapoptotic effects.Moreover,melatonin significantly ameliorated acrylamide-caused histopathological changes in kidney tissue.Conclusions:Melatonin attenuates acrylamide-induced renal oxidative stress,inflammation,apoptosis,and DNA damage in rats.

In vitro study of emodin-induced nephrotoxicity in human renal glomerular endothelial cells on a microfluidic chip

Emodin is an effective component of rhubarb with positive pharmacological effects on human health.However,it is also toxic to different cells or tissues to varying degrees.The effects of emodin on glomerular endothelial cells(GECs)remain to be tested,and the documented works were always performed in vitro and hardly reflect the real physiological situation.To study the effects of emodin on GECs in a biomimetic environment,we utilized a microfluidic chip to assess the physiological reaction of human renal glomerular endothelial cells to various concentrations of emodin in this work.The results showed that emodin caused cytotoxicity,impaired glomerular filtration barrier integrity to macromolecules,and increased barrier permeability in a dose-dependent manner.With the increase in emodin concentration,the concentration of the pro-inflammatory cytokine tumor necrosis factor-α,interleukin(IL)-6,transforming growth factor-β1,and monocyte chemoattractant protein(MCP-1)increased while the production of inflammatory cytokine IL-6 first increased and then decreased with the increase in emodin concentration.Our findings shed new light on emodin-induced nephrotoxicity and provide insights for the application of microfluidic chip devices to reveal drug-cell interactions.

Reflections on the Toxicity and Safety of Traditional Chinese Medicine Combined with the Cases of Nephrotoxicity and Hepatotoxicity

This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.

Licorice Extracts Attenuate Nephrotoxicity Induced by Brucine Through Suppression of Mitochondria Apoptotic Pathway and STAT3 Activation

Licorice,one of the most widely used medicinal herbs in East Asia,has effects such as anti-inflammation,antioxidant,and detoxifying.This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity.Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice.The content of blood urea nitrogen and creatinine in serum,the activities of superoxide dismutase and content of glutathione,malonaldehyde in kidney tissue were detected.Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney.The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis.The results illustrated that treatment with licorice extracts(LE)significantly protected against the brucineinduced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine,attenuating pathologic damage.The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione,promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde.In addition,LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3(STAT3)activation.Taken together,these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway.More importantly,the renoprotective effects may be mediated,at least partly,by preventing the activation of STAT3 protein.

Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity:Characterization and evaluation

Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.

Toxicity Evaluation of Freshwater Cyanobacterium Microcystis aeruginosa PCC 7806: Ⅱ Nephrotoxicity in Rats

Nephrotoxic potential of laboratory cultures of freshwater cyanobacterium (blue-green al ga) Microcystis aeruginosa PCC 7806 (Pasteur Institute) was assessed in male rats. The ani mals were injected intraperitoneally with 0. 5, 1. 0 and 2. 0 LD50 doses of lyophilized cell ex tract. Elevated plasma urea and creatinine levels were accompanied by decrease in protein and albumin levels, followed by hematuria, proteinuria and bilirubinuria. Also decrease in kidney lactate dehydrogenase and glutamic oxaloacetic transaminase indicated possible nephrotoxic po tential of the cyanobacteria. The extract also produced various hematological changes associat ed with stagnant type of hypoxia. High perfomance liquid chromatography of the culture I dentified the active principle (toxin) as Microcystin-LR

Nephrotoxicity in cancer treatment:An overview

Anticancer drug nephrotoxicity is an important and increasing adverse drug event that limits the efficacy of cancer treatment.The kidney is an important elimination pathway for many antineoplastic drugs and their metabolites,which occurs by glomerular filtration and tubular secretion.Chemotherapeutic agents,both conventional cytotoxic agents and molecularly targeted agents,can affect any segment of the nephron including its microvasculature,leading to many clinical manifestations such as proteinuria,hypertension,electrolyte disturbances,glomerulopathy,acute and chronic interstitial nephritis,acute kidney injury and at times chronic kidney disease.The clinician should be alert to recognize several factors that may maximize renal dysfunction and contribute to the increased incidence of nephrotoxicity associated with these drugs,such as intravascular volume depletion,the associated use of nonchemotherapeutic nephrotoxic drugs(analgesics,antibiotics,proton pump inhibitors,and bonetargeted therapies),radiographic ionic contrast media or radiation therapy,urinary tract obstruction,and intrinsic renal disease.Identification of patients at higher risk for nephrotoxicity may allow the prevention or at least reduction in the development and severity of this adverse effect.Therefore,the aim of this brief review is to provide currently available evidences on oncologic drug-related nephrotoxicity.

Thyme oil and thymol abrogate doxorubicin-induced nephrotoxicity and cardiotoxicity in Wistar rats via repression of oxidative stress and enhancement of antioxidant defense mechanisms

This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin(DOX)-induced renotoxicity,cardiotoxicity,and oxidative stress in Wistar rats.Thyme oil was subjected to GC-MS analysis,which indicated that thymol was the major constituent representing 33.896%.Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent,thymol,at doses 250 and 100 mg/kg b.w./every other day,respectively,by oral gavage for the same period.Thyme oil and thymol markedly ameliorated the raised levels of serum urea,uric acid,and creatinine in DOX-administered rats.They also reduced the elevated activities of serum CK-MB and LDH.Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats,thereby reflecting its more potent effect on kidney and heart functions.Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol.The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft,inflammatory cells infiltration,protein cast in lumina of the renal tubule,and thickening of the parietal layer of Bowman’s capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol;thyme oil was more effective.In addition,DOX-induced deleterious heart histological alterations,including intramuscular infiltration of inflammatory cells,focal necrosis of cardiac myocytes,and edema,were remarkably reduced by treatment with thyme oil and thymol.Thus,it can be concluded that DOX could induce marked toxicity in kidney and heart,and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.

Microproteinuria for detecting calcineurin inhibitor-related nephrotoxicity after liver transplantation

AIM： To investigate whether microproteinuria could be used as an early and sensitive indicator to detect calcineurin inhibitor （CNI）-related nephrotoxicity after liver transplantation.METHODS： All liver transplant recipients with normal serum creatinine （SCr） and detectable microproteinuria at baseline were included in this study. The renal function was monitored by the blood clearance of 99mTc-diethylenetriaminepentaacetic acid every 6 mo. Microproteinuria, SCr and blood urea nitrogen （BUN） were measured at entry and at subsequent follow-up visits. The patients were divided into different groups according to the mean values of glomerular filtration rate （GFR） at the follow-up time points： Group 1, GFR decreased from baseline by 0%-10%; Group 2, GFR decreased from baseline by 11%-20%; Group 3, GFR decreased from baseline by 21%-40%; Group 4, GFR decreased from baseline by 〉 40% and/or SCr was increasing.RESULTS： A total of 143 patients were enrolled into this study （23 females and 120 males）. The mean follow-up was 32 mo （range 16-36 mo）. Downward trends in renal function over time were observed in the study groups. SCr and BUN increased significantly only in Group 4 patients （P 〈 0.001）. β2-microglobulin （β2m） and al-microglobulin （αlm） significantly increased with the subtle change of renal function in recipients who were exposed to CNI-based immunosuppression regimens. The reductions in GFR were closely correlated with elevated cclm （P = -0.728, P 〈 0.001） and β2m （r2 = -0.787, P 〈 0.001）.CONCLUSION： β2m and α1m could be useful as early and sensitive indicators of CNI-induced nephrotoxicity.

Nephroprotective activity of Solanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents

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.

Naringin attenuates oxidative stress,inflammation,apoptosis,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats

Objective:To explore the possible effects of naringin on acrylamide-induced nephrotoxicity in rats.Methods:Sprague-Dawley rats weighing 200-250 g were randomly divided into five groups.The control group was given intragastric(i.g.)saline(1 mL)for 10 d.The acrylamide group was given i.g.acrylamide in saline(38.27 mg/kg titrated to 1 mL)for 10 d.The treatment groups were administered with naringin in saline(50 and 100 mg/kg,respectively)for 10 d and given i.g.acrylamide(38.27 mg/kg)1 h after naringin injection.The naringin group was given i.g.naringin(100 mg/kg)alone for 10 d.On day 11,intracardiac blood samples were obtained from the rats when they were under anesthesia,after which they were euthanized.Urea and creatinine concentrations of blood serum samples were analyzed with an autoanalyzer.Enzyme-linked immunosorbent assay was used to quantify malondialdehyde,superoxide dismutase,glutathione,glutathione peroxidase,catalase,tumor necrosis factor-α,nuclear factor-κB,interleukin(IL)-33,IL-6,IL-1β,cyclooxygenase-2,kidney injury molecule-1,mitogen-activated protein kinase-1,and caspase-3 in kidney tissues.Renal tissues were also evaluated by histopathological and immunohistochemical examinations for 8-OHdG and Bcl-2.Results:Naringin attenuated acrylamide-induced nephrotoxicity by significantly decreasing serum urea and creatinine levels.Naringin increased superoxide dismutase,glutathione,glutathione peroxidase,and catalase activities and decreased malondialdehyde levels in kidney tissues.In addition,naringin reduced the levels of inflammatory and apoptotic parameters in kidney tissues.The histopathological assay showed that acrylamide caused histopathological changes and DNA damage,which were ameliorated by naringin.Conclusions:Naringin attenuated inflammation,apoptosis,oxidative stress,and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats.

Melamine Nephrotoxicity is Mediated by Hyperuricemia

Objective We tested whether melamine nephrotoxicity was exacerbated by urate(a typical component of renal stones in humans)in rats with hyperuricemiainduced by the uricase inhibitor,potassium oxonate(Oxo).Methods Rats were exposed to melamine or Oxo alone or combinations of melamine(200-400 mg/kg)and Oxo(200-600 mg/kg)for 3 consecutive days.Kidney injury was evaluated by renal biochemical functions,histomorphology,and lipid peroxidation.Kidney crystals were analyzed for their composition.Results Nephrotoxicity was minimal in animals administered melamine or Oxo alone,but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined.All rats in the 400+600(melamine+Oxo)and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days;no rat died in the 200+400 or 200+200 mg/kg group.Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds.Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys,resembling human stones.Conclusion Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans.Future studies should consider uric acid together with melamine when examining adverse effects in humans.

Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients

AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008.We investigated patients who had shown acute renal failure(ARF),and examined their clinical characteristics,laboratory data,use of preventive measures,treatment cycles,the amount of cisplatin administered,recovery period,subsequent treatments,and renal status between the recovered and unrecovered groups.RESULTS:Forty-one of the 552 patients had serum creatinine(SCR)levels greater than 1.5 mg/dL.We found that pre-ARF SCR,ARF SCR,and ARF glomerular filtration rates were significantly associated with renal status postARF between the two groups(P=0.008,0.026,0.026,respectively).On the receiver operating characteristic curve of these values,a 1.75 mg/dL ARF SCR value had 87.5%sensitivity and 84.8%specificity(P=0.011).CONCLUSION:Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.

Nephroprotective effect of Murraya koenigii on Cyclophosphamide induced nephrotoxicity in rats

Objective: To evaluate the nephroprotective effect of defatted mehtanolic extract and aqueous extract of Murraya koenigii against Cyclophosphamide drug. Methods: Nephrotoxicity was induced by Cyclophosphamide in 7 d at 150 mg/kg body weight through intraperitoneal route in rat model. Nephroprotective activity of Murraya koenigii(M. koenigii) extract(100 mg/kg and 200 mg/kg in intraperitoneal route) was measured, including nephrological source, oxidative stress parameters like superoxide dismutase, glutathione, the lipid peroxide and in vivo assay like blood urea nitrogen, creatinine were determined and analyzed by One way analysis of variance followed by Tukey's test. Results: The study result showed that important phytochemicals such as carbohydrates, flavonoids, tannin, alkaloids, glycosides, protein and steroids were found to be present in the extract of M. koenigii. The renal function markers like blood urea nitrogen and ceatinine level were found to be decreased significantly by M. koenigii extract treatment. A significant difference was found to be at P<0.01. Conclusions: The present study reveals the protective role of M. koenigii extract against Cyclophosphamide induced nephrotoxicity.

Nephrotoxicity and carcinogenesis of aristolochic acids and their derivates

Aristolochic acids （AAs）, a natural mixture of 8-methoxy-6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAI）and 6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAII）, derived from aristolochiaceae species, has beenreported to cause AAS-induced nephropathy and upper urothelial cancer. In this review, we summarize the informationon the nephrotoxicity and carcinogenesis of AAs and their derivatives. AAs nephrotoxicity can lead to apoptosis andoxidative stress of renal tubular cells, and inhibition of the expression of aquaporins. AAs can also reduce the capabilityfor renal tubular epithelial cell repair after acute injury and further produce renal fibrosis by activating TGF-β-Smadsignaling and promoting the migration of macrophages. Moreover, AAs-induced carcinogenesis may be due to theformation of covalent adducts with DNA which can lead to the mutation in certain tumor suppressor genes orproto-oncogenes and the different catalyzing capacity of the microsomal cytochrome P450 of individuals in AAImetabolism.

Nephroprotective Effect of <i>Nigella Sativa</i>and <i>Matricaria Chamomilla</i>in Cisplatin Induced Renal Injury—Supportive Treatments in Cisplatin Nephrotoxicity

Nigella sativa and Matricaria chamomilla are extensively consumed as tea or tonic. Despite their widespread use as a home remedy, relatively few trials evaluated their benefits in nephroprotection. Hence, this study evaluates the nephroprotective effects of supportive treatments (N. sativa, M. chamomilla and vitamin E) in cisplatin nephrotoxicity rat model. Eighty rats divided into 10 groups, of 8 animals each. The first group (G1) injected with saline intra-pretoneal (i.p). G2 injected with 5 mg/kg cisplatin i.p on zero day of experiment and repeated 4 times, with 5 days free interval. G3-G10 received daily supportive treatments, started 5 days before the experiment (–5day). Concomitantly G4, G6, G8 and G10 injected with 5 mg/kg cisplatin i.p like G2. On day sixteen, animal scarified, serum and/or kidney tissue were used to determine kidney function tests (serum urea, creatinine, NAG, β-gal), oxidative stress indices (NO, LPO), antioxidant activities (SOD), sulphur compounds (GGT, GSH, total thiols ), apoptotic indices (cathepsin D, DNA fragmentation), two minerals (Ca2+ and zn2+). Cisplatin caused marked elevation in serum GGT that reduced signifi-cantly in group received M. chamomilla with cisplatin (P < 0.001). There is a correlation between GGT and NAG in cisplatin group (r = 0.731 p < 0.05) that may suggest one of possible mechanisms of renal injury by cisplatin. M. chamomilla followed by N. sativa and vitamin E improved the biochemical and pathological renal injury, as determined by increasing the body weight, normalizing the kidney functions, decreasing the oxidative stress markers, improving the apoptotic markers, minimizing the pathological changes. Hence, N. sativa and M. chamomilla will be a promising nephroprotective agents for reducing cisplatin nephrotoxicity, most probably, by antioxidants effects and inhibition GGT production, respectively.

Cyclosporine-Associated Nephrotoxicity

Cyclosporine (CsA) has revolutionized transplant medicine and is currently one of the most important immunosuppressive agents for a wide range of organ transplantations and of autoimmune and inflammatory diseases, such as rheumatoid arthritis, uveitis, psoriasis, and atopic dermatitis. Renal impairment represents the main limitation to CsA long-term continuous therapy. However, it has been shown that nephrotoxicity is associated with longer treatment duration, larger cumulative doses and higher daily dose of CsA. With low dose regimens (<5 mg/kg/day), stable serum creatinine levels have been observed up to 15-20 years after kidney transplantation. Intermittent therapy may offer a good therapeutic strategy to limit long-term renal dysfunction, given the fact that renal structural changes are dose- and time-dependent. The best predictor of permanent renal damage is a persistent increase in serum creatinine level one month after treatment withdrawal. In patients with autoimmune diseases, the percentage increase in serum creatinine above baseline value during CsA therapy has been shown to predict CsA-induced nephropathy. Before CsA therapy initiation, patients should undergo a thorough baseline evaluation including laboratory assessments, in particular electrolytes, serum creatinine, and urea levels. Furthermore, patients should be evaluated for factors that might increase the risk of nephrotoxicity, such as obesity, older age, hypertension, concomitant use of nephrotoxic drugs, and pre-existing renal conditions. In the present paper, CsA-induced nephropathy will be reviewed in terms of pathophysiology, pathologic and clinical findings, and strategies for prevention and management.

Effect of nettle(Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits

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.

Floral extract of Tecoma stans:A potent inhibitor of gentamicin-induced nephrotoxicity in vivo

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(LD50】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.

The protective effects of Ribes diacanthum Pall on cisplatin-induced nephrotoxicity in mice

Aim Ethnopharmacological relevance： Ribes diacanthum Pall. （Saxifragaceae） , a Mongolian folk me- dicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall （RDP） against cisplatin-induced nephrotoxicity. Methods The renal injury was mod- eled by intraperitoneal injection of cisplatin for 5 consecutive days （5 mg·kg^-1 ）. Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg · kg^- 1 for 14 consecutive days, starting 7 days prior to cisplatin administration. Results We demonstrated that pretreatment with RDP aqueous ex- tract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen （BUN） and serum creatinine （Cr） levels observed in cisplatin-administrated mice. Histopatho- logical analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Fur- ther western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase （SOD）, Heine oxygenase 1 （HO-1） and catalase （CAT）, suppressed lipid peroxidation as well as reactive oxygen species （ROS） production. Conclusion We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possi- bly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotox- icity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.