Modulation of the Nrf2/HO-1 Pathway- and Apoptosis-Related Genes Following 5-hydroxymethylfurfural Induced Mouse...

Food contaminants released from heat-treated foods have been an issue of global investigation in recent years. The risk and toxicity assessment of 5-hydroxymethylfurfural (HMF), which is mostly exposed to through food consumption, is also of great importance. Studies have revealed the toxicity of HMF on various tissues and systems. However, there are not enough studies on the toxic effects of HMF on the liver. This study applied different doses of HMF (30 and 300 mg/kg) to adult mice for 21 days. Liver tissues obtained from mice exposed to HMF were examined histologically and histopathologically. The investigation of oxidative damage in HMF-induced liver tissue involved the spectrophotometric measurement of malondialdehyde, hydroxyl radicals, and hydrogen peroxide levels and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, gamma glutamyl transpeptidase, and glutathione-S-transferase. The expression levels of genes associated with the Nrf2/Keap1/HO-1 signaling pathway were examined. Furthermore, oxidative stress-related genes and important genes in the apoptotic pathway were analyzed for their expression levels. The findings indicated that HMF-induced histological alterations, including abnormalities, fatty degeneration, and inflammation in hepatocytes. Furthermore, HMF caused hepatotoxicity by negatively affecting the parameters related to oxidative stress. The results revealed that HMF elevated the expression levels of apoptotic genes in liver tissue and decreased the expression levels of antiapoptotic genes, thus promoting apoptosis. These results provide new evidence that HMF exerts its toxic effect on the liver through modulation of the Nrf2 signaling pathway and subsequent induction of oxidative stress and promotion of apoptotic processes.