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

Abstract

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 µg 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 µg 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.

Keywords:

• 4-methylimidazole (4-MI)
• oxidative stress
• inflammation
• sub-chronic toxicity
• liver

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Additional information

Funding

The deputy of research of Zanjan University of Medical Sciences supported this work (Grant NO: A-12–769-53).