4-methylimidazole can promote oxidative stress, inflammation and histopathological assessment following sub-chronic exposure in rats: mechanistic approaches

4-methylimidazole (4-MEI) as the main by-product of many foods like drink colas, beverages, soy sauce, meats, candy, vinegar and caramel color which is formed in a high temperature following millard reaction. Other data revealed that 4-MEI is a neurotoxic and carcinogenic agent in animals but the obscure mechanistic pathway on the liver of wistar rats after two month administration. Therefore, sub-chronic effects of 4-MEI (32 mu g kg-1-64 mg kg-1) were conducted on the cytotoxicity and inflammatory biomarkers in the liver and then histopathological changes were evaluated following oral administration. Our data revealed that 4-MEI exposure enhanced protein and lipid oxidation, and decreased reduced glutathione and total antioxidant level (FRAP) with histopathological changes in rats in higher doses of 320 mu g kg-1. Our data explored the potentially toxic role of 4-MEI on the liver via induction of oxidative stress, mitochondrial dysfunction with negative impacts on glutathione and Frap level, and a raise in protein carbonylation and lipid peroxidation in the different doses of 4-MEI which leads to cell death signaling in the liver. Increased nitric oxide (NO) levels suggested the involvement of inflammation in 4-MEI mechanistic toxicity. Our data explored the potential hepatotoxic of 4-MEI by considering its possible role in oxidative stress, inflammation, and mitochondrial dysfunction.