Glyphosate based-herbicide disrupts energy metabolism and activates inflammatory response through oxidative stress in mice liver.

Glyphosate, the most widely used herbicide worldwide, has been reported to cause hepatotoxicity. However, these systematic mechanisms remain poorly understood. Here, we investigated the effects of glyphosate-based herbicides (GBH) on liver toxicity in mice exposed to 0, 50, 250, and 500 mg/kg/day GBH for 30 d. Pathological and ultrastructural changes, serum biochemical indicators, oxidative stress state, and transcriptome and key protein alterations were performed to describe the hepatic responses to GBH. GBH induced hepatocytes structural alterations, vacuolation, and inflammatory, mitochondrial swelling and vacuolization; damaged liver function and aggravated oxidative stress; blocked the respiratory chain, promoted gluconeogenesis, fatty acid synthesis and elongation, and activated complement and coagulation cascades system (CCCS) in the liver. Moreover, SOD, H 2 O 2 , and MDA were negatively correlated with the CxI and CxIV genes, but positively correlated with the genes in glucolipid metabolism and CCCS pathways; however, the opposite results were observed for CAT, GSH-Px, and T-AOC. Overall, this study revealed the systematic mechanism underlying hepatotoxicity caused by GBH, providing new insights into understanding the hepatotoxicity of organophosphorus pesticide. [Display omitted] • GBH triggers oxidative stress, further disturbs energy metabolism and activates inflammatory response in the liver. • GBH blocks mitochondrial OXPHOS, promotes glucolipid metabolism, finally leading to liver dysfunction. • GBH increases the release of inflammatory mediators, finally promoting liver cavitation. • Systematic molecular regulatory network of GBH-induced hepatotoxicity was built. [ABSTRACT FROM AUTHOR]