1,3-二氯-2-丙醇诱导小鼠肾小管细胞凋亡和铁死亡的体内外实验研究OA

1,3-dichloro-2-propanol(1,3-DCP)is a food contaminant formed during food processing.Studied have shown that long-term exposure to 1,3-DCP can induce nephrotoxicity,but the underlying mechanism remains incompletely understood and requires further investigation.In this study,male C57BL/6J mice were orally administered 1,3-DCP at different doses(12.5,25,50 mg·kg-1)by gavage for 30 consecutive days.Renal pathology changes were observed by hematoxylin-eosin(HE)staining.The expression levels of apoptosis-related proteins(Cytochrome c,Bax,Bcl-2,Caspase3)and ferroptosis-related proteins(GPX4 and ACSL4)were analyzed by Western blot.NRK-52E cells were used to further explore the mechanism of 1,3-DCP-induced nephrotoxicity.Cells were pretreated with 10 μM apoptosis inhibitor Z-VAD-FMK to examine changes in apoptosis;10 μM ferroptosis inhibitor Fer-1 to examine changes in ferroptosis;and 5 mM reactive oxygen species(ROS)inhibitor NAC,followed by Western blot analysis of the expression of key proteins involved in apoptosis and ferroptosis.In vivo results showed that,compared with the control group,1,3-DCP mainly caused pathological damage in mouse renal tubules,significantly up-regulated the expression of Cleaved Caspase3,Pro-Caspase3,Cytochrome-c,Bax,and ACSL4,and down-regulated the expression of Bcl-2 and GPX4.In vitro results showed that,compared with the 1,3-DCP group,the 1,3-DCP+Z-VAD-FMK group exhibited increased cell viability and decreased expression of Cleaved Caspase3 and Pro-Caspase3;1,3-DCP+Fer-1 group protein levels showed increased cell viability,elevated GPX4 expres-sion,and reduced ACSL4 expression;the 1,3-DCP+NAC group displayed increased cell viability,decreased expression of Cleaved Caspase3,Pro-Caspase3,and ACSL4,and increased GPX4 expression.These findings suggest that 1,3-DCP may induce apoptosis and ferroptosis in mouse renal tubular cells through ROS.