Glycidol-induced hepatocyte apoptosis via endoplasmic reticulum stress: The underlying role of the gut-liver axis

Abstract

Glycidol (CAS: 556-52-5), a known carcinogen and genotoxicant, is often found in refined vegetable oils. Human exposure predominantly occurs through consumption of these oils and their byproducts, which contain glycidyl esters (GEs). Upon ingestion, GEs are metabolized to release glycidol, posing substantial health hazards. Historical studies have reported the tumorigenic properties of glycidol across various organs in mice models, encompassing the stomach, liver, lungs, brain, mammary gland, and skin. In this study, we employed a Balb/c mice model to investigate the hepatotoxic effects of glycidol following exposure to escalating doses (0, 25, 50, and 100 mg/kg bw/day). The hepatotoxicity was evidenced by a significant elevation in liver enzymes (ALT, AST), indicative of liver cell damage. Furthermore, biochemical analysis revealed heightened levels of oxidative stress indicators (SOD, MDA, GSH) and the upregulation of endoplasmic reticulum stress proteins, underscoring the cellular stress response. The induction of hepatocyte apoptosis served as a direct marker of liver damage caused by glycidol exposure. Additionally, glycidol altered the composition of intestinal microbiota and short-chain fatty acids (SCFAs), which unbalanced homeostasis. Gut barrier integrity markers (ZO-1, Claudin-1, Occludin, TLR4, LPS) indicated increased permeability of harmful substances to the liver via the gut-liver axis, which exacerbated hepatic injury. These findings highlight glycidol's disruption of gut homeostasis and its hepatotoxic potential.