Methylamphetamine Induces HK-2 Cells Injury Via Oxidative Stress/autophagy/apoptosis Pathway

Objective: This study aims to explore the role and potential mechanism of methamphetamine(meth)exposure induced renal tubular epithelial cells(HK-2 cells)injury in vitro,and to elucidate the relationship among oxidative stress,autophagy and apoptosis of HK-2 cells after methamphetamine exposure were elucidate.Methods: The injury models of renal tubular epithelial cells exposed to different concentrations of methamphetamine(0 μm,100 μm,300 μm,900 μm)were established;the related inflammatory factors(TNF-α,IL-1 β and IL-6)were detected by enzyme-linked immunosorbent assay(ELISA);CCK8 method and 2 ’,7 ’-dichlorofluorescein diacetate were used to detect the cell viability and oxidative stress after methamphetamine treatment,and western blot was used to detect the changes of protein expression of oxidative stress,autophagy and apoptosis after methamphetamine treatment.The changes of autophagy and apoptotic proteins were detected after methamphetamine treatment.Results: The in vitro model of kidney was established by methamphetamine,which was identified by KIM-1 and NGAL expression.With the increase of methamphetamine concentration,the toxicity to renal tubular epithelial cells was more evident;moreover,the cell viability of renal tubular epithelial cells was gradually decreased,while the level of oxidative stress gradually increased;autophagy related proteins(p-m TOR,Beclin1,p62 and lc3b)and apoptosis related proteins(PARP,p-m TOR,Beclin1,p62 and Lc-3b)were increased.Meanwhile,the expression of Bax and BCL2 increased significantly,and the level of oxidative stress,autophagy and apoptosis of renal tubular epithelial cells were significantly inhibited after the addition of oxidative stress inhibitors.Conclusion: The toxicity of methamphetamine on renal tubular epithelial cells was dose-dependent;methamphetamine promoted the injury of renal tubular epithelial cells mainly through autophagy abnormality and oxidative stress.