2-Amino-3-methylimidazo[4,5-f]quinoline induced oxidative stress and inflammation via TLR4/MAPK and TLR4/NF-κB signaling pathway in zebrafish (Danio rerio) livers

Abstract

2-Amino-3-methylimidazole[4,5-f]quinoline (IQ) is a harmful substance, mainly existing in protein-abundant thermally processed foods and polluted environments. This study investigated the hepatotoxicity of IQ by exposing zebrafish model organisms at 0, 8, 80, and 800 ng/mL concentrations for 35 days and was supposed to reveal the mechanism of IQ-induced oxidative stress and inflammation in the liver. The results showed that, after IQ exposure, alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), and malondialdehyde (MDA) levels in zebrafish liver increased significantly; meanwhile, significantly increased tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-12 (IL-12) levels induced severe oxidative stress and inflammation; however, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione s-transferase (GST) and glutathione peroxidase (GSH-Px) levels significantly decreased. The results indicated that the increased IQ exposure gradually aggravated pathological changes of zebrafish liver tissue (irregular cell morphology, cytoplasmic vacuolation, and inflammatory cell infiltration) and induced significant liver damage at last. Alterations in the expressions of genes and proteins involved in the IQ-induced TLR4/MAPK and TLR4/NF-κB pathways can elucidate the mechanism of its hepatotoxicity. The study provides evidence of IQ-induced hepatotoxicity and helps to draw attention to the health risks of dietary and environmental exposure to IQ.

Keywords: Hepatotoxicity; IQ; Inflammation; MAPK/NF-κB; Oxidative stress.