The role of ER stress and ATP/AMPK in oxidative stress meditated hepatotoxicity induced by citrinin

• DOI: 10.1016/j.ecoenv.2022.113531
• Publication Date: 2022-04-25T15:52:08Z
• Authors: Jing Wu; Chenglin Yang; Mengran Yang; Zengenni Liang; You Wu; Xiangyi Kong; Hui Fan; Siqi Wang; Can Ning; Wenguang Xiao; Ye Jin; Jine Yi; Zhihang Yuan
• Keywords: Citrinin

Citrinin, a secondary metabolite, can pose serious risks to the environment and organisms, but its hepatotoxic mechanisms are still unclear. Histopathological ultrastructural results showed that citrinin-induced liver injury in Kunming mice, mechanism of hepatotoxicity was studied L02 cells. Firstly, citrinin mades cell cycle arrest G2/M phase by inhibition cyclin B1, D1, cyclin-dependent kinases 2 (CDK2), CDK4 expression. Secondly, inhibits proliferation promotes apoptosis cells via disruption mitochondria membrane potential, increase Bax/Bcl-2 ration, activation caspase-3, 9, enhance lactate dehydrogenase (LDH) release. Then, superoxide dismutase (SOD) activity increases accumulation malondialdehyde (MDA) reactive oxygen species (ROS), resulting oxidative damage cells; upregulates protein expression binding immunoglobulin (Bip), C/EBP homologous (CHOP), PKR-like ER kinase (PERK) activating transcription factor6 (ATF6), inducing stress phosphorylation AMP-activated (AMPK) decreases content adenosine-triphosphate (ATP), AMPK pathway Eventually, pretreatment with NAC, an ROS inhibitor, alleviates inhibiting ROS-mediated stress; 4-PBA, reversed p-AMPK; dorsomorphin, apoptosis. In summary, induces aggravate ROS-ER stress-AMPK signaling pathway.