Investigation Of Taurine's Protection Against As₂O₃-induced Autophagy In Livers Of Rats' Offsprings

Objective: Arsenic is one of the environmental pollutants present in nature.Inorganic arsenic exposure can cause many chronic diseases.In the pathogenesis of inorganic arsenic,arsenic causes the generation of reactive oxygen species?ROS?,resulting in tissue damage.It is the most widely accepted mechanism.Nrf2-Trx is a key factor in cell oxidative stress response and has antioxidant activity.Autophagy is the process of mitochondrial mitochondrial regeneration by mitochondrial biogenesis,through mitochondrial chaperones and mitochondrial enzymes control mitochondrial protein quality,so as to achieve the balance of the number of healthy mitochondrial process,but the disorder of autophagy can cause tissue damage.Studies have shown that arsenic can cause autophagic death of INS-1 cells,but the mechanism needs further study.Taurine is naturally occurring in the nature of antioxidants.In this study,we investigated whether taurine can interfere with the arsenic-induced offspring rats pancreatic autophagic injury through the Nrf2-Trx pathway.Method: To investigate the effects of As₂O₃ on offspring rats,the pregnant Wistar rats were randomly divided into five groups,and the rats were treated with 0mg/kg BW⁸ mg/kg BW As₂O₃,the group 5 was given 8 mg/kg BW As₂O₃ after pretreatment with taurine.The rats were given by gavage once a day to the offspring weaning.The offsprings was treated as its mother until sexual maturity,totally 57 days.We observed the morphology of rat by HE staining.To observe the formation of autophagosome in pancreatic cells of offspring rats,we used the electronic microscopy and counted the number of the autophagosome.The expressions of Nrf2,LC3 protein in the pancreaticof offspring rats were detected by Western blot.We used RT-PCR to detect the expression of Trx gene.We used MDA kit to measure the level of MDA in the pancreaticof offspring rats.Results: HE staining showed that,the size of pancreatic cells and islets were significantly reduced with the increase of the concentrations of arsenic and after treatment with taurine the size of the cell was increased.Quantification of the autophagosomes numbers per cell demonstrated that As₂O₃ increased autophagosomes number significantly and in a dose-dependent manner.The number of autophagosomes in As₂O₃-treatedrats was obviously decreased after pretreatment with taurine.The level of LC3-II was increased dramatically in As₂O₃-treated pancreatics.After pretreatment with taurine,the expression of LC3-II was decreased.The expression of Nrf2 protein,Trx gene and the level of MDA was decreased in offsprings' pancreatics.Taurine could reverse arsenic-inhibited Nrf2-Trx and inhibit autophagy.Conclusion: As₂O₃ could induce autophagy in offspring pancreatics;the inhibition of Nrf2-Trx contributed to the As₂O₃–induced autophagy in offspring pancreatics;Taurine protects against As₂O₃-induced autophagy in pancreatics of rats through Nrf2-Trx pathway...