Arsenic-Induced Ferroptosis in Chicken Hepatocytes Via the Mitochondrial ROS Pathway

Overview

Journal Biol Trace Elem Res

Date 2023 Dec 15

PMID 38102534

Authors

Xinglin Gao

Qian Su

Hang Pan

Yanli You

Zhiyan Ruan

Yuhan Wu

Zhaoxin Tang

Lianmei Hu

Affiliations

Soon will be listed here.

Abstract

Arsenic has been shown to be highly toxic and can cause liver damage. Previous studies have shown that arsenic causes severe liver damage and induces accumulation of reactive oxygen species (ROS). This study aimed to investigate the effects of ferroptosis on the liver in arsenic trioxide (ATO) and to explore the underlying mechanisms. We confirmed the hepatotoxic effects of arsenic by in vivo and in vitro experiments. After 28 days of administration of arsenic trioxide (4-mg/kg, 8-mg/kg) by gavage, chickens exhibited body weight loss and liver damage in a dose-dependent manner. In addition, in vivo and in vitro western blot and real-time fluorescence quantitative PCR analyses simultaneously indicated that ferroptosis might be the main pathway of arsenic-induced liver injury. Finally, Mito-TEMPO effectively eliminated the ROS accumulation in mitochondria, significantly attenuating the process of cellular ferroptosis. In summary, the hepatotoxic effects of arsenic are related to ferroptosis, and the hepatic ferroptosis process of arsenic is regulated by mitochondrial ROS (MtROS). Our study reveals new mechanisms of arsenic toxicity to the liver, which may deepen our understanding of arsenic toxicology.

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