Lycopene, quercetin, and silymarin alleviate tartrazine-induced liver injury via modulating Nrf2 signaling and endoplasmic reticulum stress pathways.

Tartrazine is a synthetic lemon-yellow azo dye that is widely used as a coloring agent in food products, drugs, and cosmetics. Tartrazine was reported to induce hepatotoxicity, however, the effects of tartrazine on nuclear factor erythroid two-related factor two (Nrf2) signaling and endoplasmic reticulum (ER) stress pathways in rat liver have not been investigated. Therefore, this study aimed to investigate the effects of tartrazine on Nrf2 signaling and ER stress pathways in rat liver, to examine the potential therapeutic effects of lycopene, quercetin, and silymarin, and to investigate the mechanisms through which they may mitigate tartrazine-induced liver injury. Rats were allocated into five experimental groups including a normal control group and a tartrazine group that received tartrazine (10 mg/kg) orally for 13 weeks. The lycopene, quercetin, and silymarin groups received tartrazine (10 mg/kg) for 13 weeks and were treated with lycopene (10 mg/kg), quercetin (50 mg/kg), and silymarin (150 mg/kg), respectively, for the last 8 weeks. Tartrazine-induced liver injury was characterized by increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase serum levels and histopathological changes in the liver. Furthermore, tartrazine suppressed hepatic Nrf2 signaling and induced ER stress. Hepatic levels of malonaldehyde and caspase-3 were increased, while the levels of superoxide dismutase activity and glutathione and B cell lymphoma-2 were decreased. Moreover, hepatic transforming growth factor-beta one levels and collagen deposition were increased. Treatment with lycopene, quercetin, and silymarin ameliorated the tartrazine-induced changes, upregulated Nrf2 signaling and alleviated ER stress. Our findings suggest that lycopene, quercetin, and silymarin may provide a promising therapeutic approach against tartrazine-induced liver injury.