Endoplasmic reticulum stress-mediated autophagy activation attenuates fumonisin B1 induced hepatotoxicity in vitro and in vivo

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
Mahendra Pal Singh, Sun Chul Kang

Abstract

Although pathological characteristics of fumonisin B1 are known to induce hepatic injury over prolonged periods, the cellular defense mechanisms against the detrimental effects of FB1 are still unknown. The underlying mechanisms of FB1 toxicity are thought to be related with the inhibition of ceramide synthase, causing an accumulation of sphingoid bases, which in turn cause development of oxidative stress. Herein, we investigated whether autophagy, a cellular defense mechanism, protects liver cells from FB1 exposure. To accomplish this, we utilized HepG2 cells and a mouse model to study the effects of FB1 in the autophagy pathway. FB1 was capable of inducing autophagy via the generation of ROS, induction of endoplasmic reticulum stress, phosphorylation of JNK, suppression of mTOR and activation of LC3I/II in HepG2 cells and mice livers. Treatment of HepG2 cells with the ROS scavenger N-acetyl-l-cysteine alleviated ER stress stimulation and induced HepG2 cell death. Moreover, suppression of autophagy with 3-Methyladenine enhanced HepG2 cells apoptosis. Concurrently, four consecutive days exposure of mice livers to FB1 altered the levels of sphingoid bases, hepatic enzymes and induced histopathological changes. Moreover, the expr...Continue Reading

Citations

May 23, 2018·Journal of Biochemical and Molecular Toxicology·Sang Ho KimSun Chul Kang
Jan 12, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Jia ChenKamil Kuca
Dec 7, 2020·Clinica Chimica Acta; International Journal of Clinical Chemistry·Kai HouXuping Qin
Feb 9, 2021·Journal of Environmental Science and Health. Part C, Toxicology and Carcinogenesis·Ruth Nabwire Wangia-Dixon, Kizito Nishimwe
Feb 7, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Lili HouKehe Huang
Feb 20, 2021·Critical Reviews in Toxicology·Thilona ArumugamAnil A Chuturgoon
Jan 1, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Song YuAibo Wu
Aug 5, 2021·Critical Reviews in Food Science and Nutrition·Haonan RuanMeihua Yang
Aug 14, 2021·Ecotoxicology and Environmental Safety·Yue WangShao-Chen Sun

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