The Experimental Study On The Serum TAS And The Action Of Methylprednisolone Therepy In Mice With Paraquat Poisoning

Paraquat (PQ) has been a widely used herbicide in many countries since the1960s.From70s, its high toxicity has been reported in animals as well as in human.Mthylprednisolone is widely practiced, but evidence for efficacy is very weak.The highmortality rate observed following paraquat exposure has been attributed to the lack ofan antidote or effective treatment to ameliorate the toxic effects of the poison. Paraquatinduced toxicity is a manifestation of its ability to undergo an alternative reduction andreoxidation known as redox cycling and subsequent generation of reactive oxygenspecies(ROS), which disrupt the prooxidative/antioxidative balance in the body,causeoxidative damage to lipids, proteins, and DNA,and lead to cell and tissueDysfunction.Despite recognizing the importance of oxidative stress as a mechanism ofparaquat toxicity,limited studies exist regarding the variation of total antioxidant status(TAS) and the effect of high doses of methylprednisolone administration in patientswith paraquat poisoning.This study was designed to evaluate the serum TAS and theaction of high doses of methylprednisolone in mice with paraquat poisoning.PartⅠThe study on changes in serum total antioxidant status of micepoisoned with paraquat by ip injectionObjective: The purpose of this study was to evaluate the serum TAS of micepoisoned with paraquat by ip injection.Methods: The mice were randomLy divided into control groups and PQgroups.The mice in PQ groups were divided into6subgroups, which received50,70,100,150,200,and300mg/kg, respectively, of paraquat by i.p. injection. The bloodsamples were taken not only from control group but also from PQ group at1h and3h,respectively, after exposure,in order for the comparative study of ABTS radicalscavenging activity. Blood samples of5mice were taken at each blood sampling point.Results:1.The serum ABTS free radical scavenging activities at either1h or3h after PQ administration in PQ subgroups were significantly lower than in controlgroup(P＜0.05).2. There was no significant difference in the serum ABTS free radicalscavenging activities in blood samples between the two studied sampling times afterexposure to the same dose of PQ(P＞0.05).3.There was no significant correlationbetween the exposure dose and the serum ABTS free radical scavenging activities ateither1h or3h after PQ administration.Conclusion: The serum ABTS free radical scavenging activities were reduced andthe serum total antioxidant status was lowed for the mice after PQ administration. Thedifference was not significant between1h value and3h value after PQ administration.PartⅡThe effescts of early use of methylprednisolone on the serum totalantioxidant status in the mice with paraquat poisoningObjective: This study was designed to evaluate the effescts of early use ofmethylprednisolone on the serum total antioxidant status in the mice with paraquatpoisoning.Methods: The mice were randomLy divided into control group,PQ group, PQ+medrol group and medrol group. The mice in PQ group were divided into6subgroups,which received50,70,100,150,200,and300mg/kg, respectively, of paraquat by i.p.injection. The mice in PQ+medrol group all received200mg/kg of methylprednisoloneby i.p. injection immediately after receiving50,70,100,150,200,and300mg/kg,respectively, of paraquat by i.p. injection. The mice in medrol group only received200mg/kg of methylprednisolone by i.p. injection. The blood samples were taken notonly from control group but also from PQ group, PQ+medrol group and medrol group at1h and3h,respectively, after exposure for the comparative study of ABTS radicalscavenging activity. Blood samples of5mice were taken at each blood sampling point.Results:1.The serum ABTS free radical scavenging activities at either1h or3hafter PQ administration in PQ group and PQ+medrol group were significantly lowerthan in control group(P＜0.05).2. There was no significant difference in the serumABTSfree radical scavenging activities in blood samples between1h value and3h value afterexposure to the same dose of PQ for PQ group and PQ+medrol group,respectively(P ＞0.05).3.There was no significant difference in the serum ABTS free radical scavengingactivities in blood samples between control group and medrol group at1h and3h,respectively after exposure to PQ(P＞0.05).4.In PQ+medrol group, there was nosignificant correlation between the exposure dose and the serum ABTS free radicalscavenging activities at either1h or3h after PQ administration.Conclusion:The study confirmed paraquat can disrupt the peroxidation/antioxidantbalance in the body, but it failed to prove that the early use of high doses ofmethylprednisolone can improve the serum total antioxidant status of the mice with PQpoisoning.PartⅢThe high-dose methylprednisolone could accelerate mortality in micewith acute paraquat poisoning:Apreliminary StudyObjective: In this study, the effects of methylprednisolone pulse therapy on micewith acute paraquat poisoning were evaluated,in order to determine if glucocorticoidscould accelerate mortality in the mice with acute paraquat poisoning.Methods:30mice in poisoning group were randomLy divided into6groups,which received50,70,100,150,200,and300mg/kg/d, respectively, of paraquat by i.p.injection. After recieving the same treatment as poisoning group,each of30mice intreatment group received200mg/kg of methylprednisolone by i.p. injection.5mice inMedrol control group only received200mg/kg of methylprednisolone by i.p. injection.Symptoms of poisoning in mice were observed and the LD50values between poisoninggroup and treatment group were compared.Results: The times o f movement of mice reduced after paraquat administration.Before death, the mice had toxicosis symptoms of a low respirator y rate,gasping breathand flapping of nose wing, and so on.The LD50values in treatment group were smallerthan that in poisoning group at either24,48or72h after exposure to paraquat.Conclusion: A single intraperitoneal injection of high-dose methylprednisolonecould accelerate mortality in mice with paraquat poisoning.