Paradoxical systemic toxicity by inhaled paraquat poisoning: A case report

Rationale:Multi-organ failure is a symptom of paraquat poisoning,resulting in high mortality and morbidity rates.Though paraquat is widely available,poisoning through inhalation is rare.Patient’s Concern:A 37-year-old male reported to the emergency department with complaints of vomiting after an alleged history of inhalation of paraquat while at work.Diagnosis:Paraquat poisoning.Interventions:Supportive management along with multiple sessions of hemodialysis.Outcomes:Renal complications caused by paraquat were improved after multiple sessions of hemodialysis.However,the patient developed respiratory complications and later due to persistent hypoxemia and non-responsive to supportive therapy,he succumbed to his illness.Lessons:Acute kidney injury is a complication of paraquat poisoning.However,kidney involvement with the inhalational mode is rare.It is caused by reduction and oxidation cycles,as well as the formation of reactive oxygen species,necessitating hemodialysis as the treatment.Without a clear history,a specific clinical trait,or a diagnostic test,diagnosis can be difficult.Our case thus highlights the inhaled paraquat poisoning,presenting with acute kidney injury with late respiratory impairment as a consequence.

Mutual promotion of mitochondrial fi ssion and oxidative stress contributes to mitochondrial-DNAmediated infl ammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis

BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induced epithelial-mesenchymal transition(EMT)and PF.METHODS:C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro.Histological changes in the lungs were examined by hematoxylin and eosin(H&E)staining.Mitochondrial morphology was detected by MitoTracker®Deep Red FM or transmission electron microscopy(TEM).Western blotting and immunofluorescence were used to determine the expression of protein.The migration ability of the cells was detected by the cell scratch test.Mitochondrial DNA(mtDNA)levels were assessed by real-time polymerase chain reaction(PCR).Enzyme-linked immunosorbent assay(ELISA)was applied to detect cytokine levels.Superoxide dismutase(SOD)activity and the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by chemichromatometry.RESULTS:PQ exposure caused EMT and PF in vivo and in vitro.PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1(Drp1),which were accompanied by oxidative stress.Inhibiting mitochondrial fission using mitochondrial division inhibitor-1(Mdivi-1),a selective inhibitor of Drp1,attenuated PQ-induced EMT and oxidative damage.Treatment with N-acetyl-L-cysteine(NAC),an antioxidant,reduced Drp1 expression,attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF.Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release,the expression of Toll-like receptor 9(TLR9)and phosphorylation(P)-NF-κB p65 as well as cytokines(interleukin 6[IL-6],interleukin-1β[IL-1β],and tumor necrosis factor-α[TNF-α])production.CONCLUSION:Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF,which is associated with the mtDNA/TLR9/NF-κB pathway.

Paraquat Dynamics on Western Andosolic and Ferrallitic Soils of Southern Cameroon

Phytosanitary products are frequently used by agriculture worldwide and in Cameroon in particular;this with a view to protecting crops and improving agricultural yields (Riba and Silvy, 1989;Bonny, 1996;Mattews et al., 2003). There are many studies on the retention of pesticides by soils, but in Cameroon, very few studies have focused on the interaction between andosols, ferralsols and the pesticides paraquat and carbendazim, which are widely used by farmers in Foumbot and Ebolowa. The objective of this work is to provide elements of understanding on the mobility of paraquat along the profile of andosolic soils of Foumbot and ferralitic soils of Ebolowa during which the soil samples were collected. The soil samples were characterized by the analytical method in accordance with the international standards at the Research Unit of Soil Analysis and Environmental Chemistry of the University of Dschang, as recommended by Pauwels et al. (1992). The different analyses of the soil samples were carried out according to the classical procedures of the Faculty of Agronomy and Agricultural Sciences, Soil, Plant and Water Laboratory. Statistical analysis was performed. Pearson correlation tests were performed to correlate soil physicochemical properties with soil adsorption parameters;thus, it has been observed that there is a strong correlation between the CEC and the rate of organic matter. The experimental device used for this study is a block device. This study was carried out in batch mode and by varying the contact time, the pH of the solution, the mass of the soil, the concentration of the solution. The physicochemical characterizations of the soils were studied. The mineralogical analysis was carried out by X-ray and infrared diffraction. The analysis of the samples was carried out by UV-Vis absorption spectrometry. The study of the adsorption kinetics showed that the adsorption of paraquat by the soils of Foumbot NK1, NK3 and Ebolowa MIN1 is better described by the pseudo-second order kinetic model since the qe values obtained from this model are close to the experimental values. The study of the adsorption kinetics showed that the adsorption process is very fast during the first thirty minutes and medium to very slow afterwards. The half-reaction times indicate that the kinetics of pollutant accumulation is faster on the surface of fallow soil NK1 (t1/2 = 11.30 min.), followed by cultivated soil NK3 (t1/2 = 19.94 min.) and finally the bare ground of Ebolowa MIN1 (t1/2 = 264.05 min.). Three adsorption models have been studied and the isotherms are best described by the Freundlich and Dubinin-Radushkevitch model. The adsorption of paraquat by the andosolic soils of Foumbot and the ferralitic soils of Ebolowa is best described by the Freundlich model. Bare forest soil MIN1 with a depth of 25 to 50 cm better describes adsorption with a correlation coefficient R2 = 0.951 μmol/g compared to cultivated soil NK3 with a surface layer of 0 to 25 cm and finally fallows soil NK1 with a depth of 25 to 50 cm. The strong biological activity of the 25 to 50 cm deep layer of MIN1, the C/N ratio of 11.00 testifies to a good mineralization of this soil. The clay content of 45% would promote the retention of paraquat and reduce the presence of this pesticide at depth.

水稻对百草枯(Paraquat)和一些环境胁迫的交叉抗性

比较了两个水稻品种对除草剂百草枯及某些环境因子的响应,发现抗百草枯品种Lemont较敏感品种桂朝2号对强光造成的光抑制、低温与脱水诱导的光氧化均具较强的抗性.同一品种的衰老叶较功能叶对百草枯敏感,对上述逆境因子的抵抗力也较弱.Lemont较桂朝2号、功能叶较衰老叶均具较高的超氧物歧化酶(SOD)活性.因此SOD在水稻对逆境胁迫的交叉抗性中起重要作用,其活性可能作为水稻的综合抗逆性筛选指标.

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

Evaluation of gastric lavage efficiency and utility using a rapid quantitative method in a swine paraquat poisoning model

BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.

Catalytic Metalloporphyrin Protects Against Paraquat Neurotoxicity in vivo

Objective To examine the neuroprotective effects of a novel manganese porphyrin, manganese （Ill） meso-tetrakis （N,N＇-diethylimidazolium-2-yl） porphyrin （MnTDM）, in the mouse model of Parkinson＇s disease （PD） induced by paraquat （PQ）. Methods Male C57BL / 6 mice were subcutaneously injected with either saline or PQ at 2-day intervals for a total of 10 doses, MnTDM was subcutaneously injected with the PQ 2 h before treatment. Performance on the pole and swim test were measured 7 days after the last injection and animals were sacrificed one day later. Levels of dopamine （DA） and its metabolites in the striatum were measured by high-performance liquid chromatography with an electrochemical detector （HPLC-ECD）. Thiobarbituric acid （TBA） method was used to assay the lipid peroxidation product, malondialdehyde （MDA）, and the number of tyrosine hydroxylase （TH） positive neurons was estimated using immunohistochemistry. Results Pretreatment with MnTI）M significantly attenuated PQ-impaired behavioral performance, depleted dopamine content in striata, increased MDA, and dopaminergic neuron loss in the substantia nigra. Conclusions Oxidative stress plays an important role in PQ-induced neurotoxicity which can be potentially prevented by manganese porphyrin. These findings also propose a possible therapeutical strategy for neurodegenerative disorders associated with oxidative stress such as PD.

Effect of ulinastatin on paraquat-induced-oxidative stress in human type Ⅱ alveolar epithelial cells

BACKGROUND:Ulinastatin(UTI) is a urinary trypsin inhibitor extracted and purified from urine of males.This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type Ⅱ alveolar epithelial cells.METHODS:The human type II alveolar epithelial cells,A549 cells,were cultured in vitro.The A549 cells were treated with different concentrations of paraquat(200,400,600,800,1 000,1 200 umol/L) and ulinastatin(0,2 000,4 000,6 000,8 000 U/mL) for 24 hours,the cell viability was measured by cell counting kit-8 and the median lethal concentration was selected.In order to establish an in vitro model of paraquat intoxication and to determine the safe dose of ulinastatin,we calculated LD50 using cell counting kit-8 to determine the survival rate of the cells.A549 cells were divided into normal control group,paraquat group and paraquat+ulinastatin group.The levels of malondialdehyde(MDA) and myeloperoxidase(MPO) were detected by biochemistry colorimetry,while the level of reactive oxygen spies(ROS) was detected by DCFH-DA assay.RESULTS:The survival rate of A549 cells treated with different concentrations of paraquat decreased in a concentration-dependent manner.Whereas there was no decrease in the survival rate of cells treated with 0-4 000 U/mL ulinastatin.The levels of MDA,MPO,and ROS were significantly higher in the paraquat group than in the normal control group after 24-hour-exposure.And the survival rate of the paraquat+ulinastatin group was higher than that of the paraquat group,but lower than that of the normal control group.The levels of MDA,MPO,and ROS were lower than those of the paraquat group.CONCLUSION:Ulinastatin can alleviate the paraquat-induced A549 cell damage by reducing oxidative stress.

Prognostic value of plasma C-reactive protein in the evaluation of paraquat poisoning patients

Objective: To investigate the prognostic value of plasma C-reactive protein(CRP) level in patients with paraquat poisoning.Methods: This study included 162 patients with paraquat poisoning. The data of plasma paraquat, CRP level and arterial blood gas were analyzed. Cox regression analysis was applied to evaluate the risk factors of prognosis. Receiver operating characteristics curve analysis and area under curve were used to calculate the predictive power of significant variable. Differences in patient survival were determined using the Kaplan–Meier method and a log-rank test.Results: Plasma CRP level was significantly increased in non-survival patients compared with survival patients(P < 0.05), and positively correlated with plasma paraquat level(P < 0.05). Cox regression analysis revealed that plasma CRP level was an independent prognostic marker of mortality within 30 days. The receiver operating characteristics curve analysis indicated that area under curve of plasma CRP level was0.867(95% CI: 0.81–0.93), and the cut-off value was 18 mg/L, and patients with CRP level over this value had a poor survival time compared with those with less than this value.Conclusions: These results suggest that plasma CRP level is distinct increased in patients with paraquat poisoning, and the plasma CRP level may be useful for the prediction of prognosis in paraquat poisoning.

Effect of SP-A/B in lipoic acid on acute paraquat poisoning

BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.METHODS: Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group(NS group), 6 rats; paraquat poisoning group(PQ group), 30 rats; and paraquat+lipoic acid treatment group(LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Whole blood(0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup(P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals(P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals(P<0.01), but the differences between different intervals in the PQ group were statistically significant(P<0.05). The differences between different intervals in the LA group were statistically significant(P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.

Analysis of Paraquat Intoxication Epidemic (2002-2011) within China

Paraquat, is a Bipy herbicide have been widely used in last decade in China. Because of its high human toxicity and mortality characteristics, paraquat has been gained considerable attention in recent years. In order to evaluate the epidemic status of paraquat harm to human health in China, 24 h hotline information about paraquat intoxication consultation from January Ist, 2002 to December 31st, 2011 was collected by experienced practitioners in the Poison Control Center （National Poison Control Center, NPCC）

Prospective experimental studies on the renal protective effect of ulinastatin after paraquat poisoning

BACKGROUND:Paraquat(PQ) is an effective herbicide and is widely used in agricultural production,but PQ poisoning is frequently seen in humans with the lung as the target organ.Currently,there are many studies on lung injury after PQ poisoning.But the kidney as the main excretory organ after PQ poisoning is rarely studied and the mechanisms of this poisoning is not very clear.In this study,we observed the expression of caspase-3 and livin protein in rat renal tissue after PQ poisoning as well as the therapeutic effects of ulinastatin.METHODS:Fifty-four Sprague-Dawley(SD) rats were randomly divided into three experimental groups:control group(group A),paraquat poisoning group(group B) and ulinastatin group(group C),with 18 rats in each group.Rats in group B and group C were administered intragastrically with 80mg/kg PQ,rats in group C were injected peritoneally with 100 000 U/kg ulinastatin once a day,while rats in group A were administered intragastrically with the same volume of saline as PQ.At 24,48,72 hours after poisoning,the expression of livin in renal tissue was detected by Westen blotting,the expression of caspase-3 was detected by immunohistochemistry,and the rate of renal cell apoptosis was tested by TUNEL detection.The histopathological changes were observed at the same time.RESULTS:Compared to group A,the expression of caspase-3 in the renal tissue of rats in groups B and C increased significantly at any time point.Compared with group B,the expression of caspase-3 in renal tissue of rats in group C decreased.Compared with group A,the expression of livin in renal tissue in rats of groups B and C increased significantly at any time point(P<0.01),especially in group C(P<0.01).TUNEL method showed that the rate of renal cell apoptosis index was higher in group B at corresponding time points than in group A(P<0.01),and was lower in group C at corresponding time points than in group B(P<0.01).CONCLUSION:UTI has a protective effect on the renal tissue of rats after paraquat poisoning through up-regulating the expression of livin and down-regulating the expression of caspase-3,but the regulation path still needs a further research.

Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and Xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(P<0.05, respectively). Moreover, interleukin(IL)-1β, IL-6 and TNF-α m RNA levels were signi? cantly higher in the paraquat group(P<0.01, respectively). However, intravenous Xuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(P<0.05, respectively).CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.

Discernment scheme for paraquat poisoning: A five-year experience in Shiraz, Iran

AIM To evaluate various schemes for paraquat poisoning and different variables that influence the outcome of acute paraquat poisoning.METHODS In a cross-sectional study, the information about all cases of acute paraquat poisoning who were admitted to teaching hospitals affiliated to Shiraz University of Medical Sciences, in a five year period(September 2010 to September 2015) were evaluated. The variables included: Demographic data, medical assessment, therapeutic options, laboratory findings, and the outcomes. Data were analyzed using SPSS, version 22. Significant difference between groups was tested using t-test for continues outcomes and χ~2 test for categorical. The significance level was considered to be P < 0.05. RESULTS A total of 104 patients(66.3% male) were evaluated. The mean age of the female patients was 22.81 ± 9.87 years and the male patients' was 27.21 ± 11.06 years. Ninety seven(93.3%) of all the cases were suicide attempts with mortality rate of 43.2%. Despite the necessity for emergency hemodialysis during the first 6 h of intoxication, none of the patients had dialysis during this time. Immunosuppressive and corticosteroid medications were not administrated in adequate dosage in 31.1% and 60% of the patients, respectively. Ingestion of more than22.5 cc of paraquat and increase in creatinine level were the most important predictors of mortality.CONCLUSION Treatment should start immediately for these patients.Moreover, creating a clinical guideline according to the findings can have an impact on the treatment procedure which seems to be necessary.

Therapeutic effects of smecta or smectite powder on rats with paraquat toxication

BACKGROUND:The plasma concentration of paraquat is closely related to the prognosis of patients with paraquat toxication,and the most common cause of death from paraquat poisoning is multiple organ failure(MOF).This study aimed to evaluate therapeutic effect of smecta on the plasma concentrations of paraquat and multi-organ injury induced by paraquat intoxication in rats.METHODS:A total of 76 healthy adult SD rats were randomly divided into group A(control group,/7=6),group B(poisoned group,n=30) and group C(smecta-treated group,n=30).Rats in groups B and C were treated intragastrically with PQ at 50 mg/kg,and rats in group A was treated intragastrically with saline(1 ml_).Rats in group C were given intragastrically smecta at 400 mg/kg 10 minutes after administration of PQ,while rats in other two groups were treated intragastrically with 1ml_ saline at the same time.Live rats in groups B and C were sacrificed at 2,6,24,48,72 hours after administration of PQ for the determination of paraquat plasma concentrations and for HE staining of the lung,stomach and jejunum.The rats were executed at the end of trial by the same way in group A.RESULTS:The plasma concentration of paraquat(ng/mL) ranged from 440.314±49.776 to4320.6150±413.947.Distinctive pathological changes were seen in the lung,stomach and jejunum in group B.Lung injuries deteriorated gradually,edema,leukocyte infiltration,pneumorrhagia,incrassated septa and lung consolidation were observed.Abruption of mucosa,hyperemic gastric mucosa and leukocyte infiltration were obvious in the stomach.The hemorrhage of jejunum mucosa,the abruption of villus,the gland damage with the addition of inflammatory cell infiltration were found.Compared to group B,the plasma concentration of paraquat reduced(P<0.01) and the pathological changes mentioned above were obviously alleviated in group C(P<0.05,P<0.01).CONCLUSION:Smecta reduced the plasma concentration of paraquat and alleviated pathologic injury of rats with PQ poisoning.

Edaravone attenuates paraquat-induced lung injury by inhibiting oxidative stress in human type Ⅱalveolar epithelial cells

BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protecting the acute injury of human type II alveolar epithelial cells(A549cells) induced by paraquat(PQ) and the change of production of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD).METHODS:A549 cells were cultured and divided into PQ group(group P),edaravone-treated group(group E) and normal control group(group C).The cells in group P were exposed to paraquat(600 umol/L),and the cells in group E were treated with edaravone(100 umol/L) additionally,and no drug intervention was given to the cells in group C.Real-time monitoring by LSCM was used to detect the cell response and the intracellular dynamic change of ROS level in A549 cells after administration of PQ and edaravone.And the levels of SOD and MDA were detected respectively by biochemistry colorimetry.Data were expressed as mean ± standard error of the mean.Statistical analysis was carried out with the soft SPSS 16.0.RESULTS:The concentration of intracellular ROS significantly increased when PQ was given to A549 cells.But after administration of edaravone,the concentration of intracellular ROS was decreased.Compared to the PQ group,the levels of SOD in the edaravone group were significantly increased while the levels of MDA were markedly decreased.CONCLUSIONS:Paraquat can increase the oxidative stress,and induce the lipid peroxidation of A549 cells.Edaravone has the effect to scavenge reactive oxygen species,and to protect against the PQ-induced lung toxicity.

Determination of Paraquat in Human Serum by HPLC

目的：建立HPLC法测定人血清中百草枯含量。方法：色谱柱：Kromasil C18柱（200mm×4．6mm，5μm），流动相：乙腈-水（含0．03mol·L-1庚烷磺酸钠，0．24mol·L-1磷酸）=3：97（用三乙胺调pH至2．0）；检测波长258nm；柱温25℃；进样体积20μl；流速0．8ml·min-1。结果：百草枯在0．106—10．6mg·L-1浓度范围内线性关系良好（r=0．9993），最低检出浓度为0．065mg·L-1。高、中、低3种浓度样品绝对回收率〉89．4％，方法回收率〉94．4％，日内精密度RSD在0．12％～1．74％之间，日间精密度RSD在0．44％～2．89％之间。结论：该方法操作简便易行、灵敏度高、专属性强，适用于百草枯的人体血清浓度测定。

Role of epithelial-to-mesenchymal transition in the pulmonary fi brosis induced by paraquat in rats

BACKGROUND:This study aims to explore the characteristics of the epithelial-to-mesenchymal transition(EMT)process and its underlying molecular mechanisms in the period of paraquat(PQ)-induced pulmonary fi brosis(PF).METHODS:Picrosirius red staining and collagen volume fraction were utilized to evaluate the pathological changes of PQ-induced PF in rats.Immunohistochemistry,Western blot,and real-time reverse transcriptase-polymerase chain reaction(RT-PCR)were used to measure the protein and gene expression of EMT markers,EMT-associated transcription factors,and regulators of EMT-related pathways,respectively.RESULTS:The collagen deposition in the alveolar septum and increased PF markers were characteristics of pathological changes in PQ-induced PF,reached a peak on day 14 after PQ poisoning,and then decreased on day 21.The protein and gene expression of the fibrosis marker,EMT markers,transcription factors,and regulators of EMT-related signaling pathways signifi cantly increased at diff erent time points after PQ poisoning compared with corresponding controls(P<0.05),and most of them reached a peak on day 14,followed by a decrease on day 21.The gene expression of EMT markers was significantly correlated with PF markers,transcription factors,and regulators of EMT-related signaling pathways(P<0.05).The mRNA expression of transcription factors was signifi cantly correlated with that of TGF-β1 and Smad2(P<0.05 or P<0.01),instead of Wnt2 andβ-catenin(P>0.05).CONCLUSIONS:EMT process plays a role in the PQ-induced PF,in which most PF and EMT markers have a peak phenomenon,and its underlying molecular mechanisms might be determined by further studies.

The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.

Antioxidant effects of aqueous extract of Salep on Paraquat-induced rat liver injury

AIM To evaluate the effects of aqueous extract of Salep on Paraquat-mediated liver injury.METHODS In this experimental study, 56 adult male Wistar rats were divided randomly to 7 groups as control, sham, and 5 experimental groups. In control group, rats did not receive any substance during experiment. In Sham group, rats were given distilled water according to their body weight and in experimental groups, Paraquat alone and with different doses of Salep aqueous extract(40, 80, 160 and 320 mg/kg) was given intraperitoneal daily for 14 d. After that, liver biochemical parameter and histologic changes were analyzed and compared in different groups. RESULTS Paraquat compared to control and sham groups, significantly(P < 0.05) increased serum level of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), bilirubin, malondialdehyde(MDA) and total oxidant capacity(TOC); while level of total protein, albumin and total antioxidant capacity(TAC) were remarkably decreased by Paraquat. Salep at doses of 80, 160 and 320 mg/kg significantly decreased serum level of ALT, AST, ALP, bilirubin, MDA and TOC and significantly increased total protein, albumin and TAC level as compared to Paraquat exposed group in dose dependent manner. Aqueous extract of Salep at doses of 40 mg/kg made no significant changes in serum level of mentioned biochemical parameters. Liver microscopic observation revealed that Paraquat could cause hepatocyte necrosis, degenerative changes, proliferation and activation of Kupffer cells(sporadically) which were reduced by Salep treatment. CONCLUSION Salep possesses remarkable hepatoprotection activity against Paraquat-induced hepatic injury by having antioxidant activity and reducing lipid peroxidation and oxidative stress.