zearalenone and Chemical-and-Drug-Induced-Liver-Injury--Chronic

Corynoline has been reported to have anti-inflammatory and antioxidative effects. In the present study, the potential protective effects of corynoline against zearalenone (ZEA)-induced liver injury were investigated. ZEA was administered daily for 5 days. Then, liver tissues were used for subsequent experiments. Corynoline attenuated liver histopathological changes induced by ZEA. The production of tumor necrosis factor-α and interleukin-1β in liver tissues, as well as aspartate aminotransferase and alanine aminotransferase in serum, was also inhibited by corynoline. Meanwhile, ZEA-induced MPO activity and MDA content were both attenuated by corynoline. ZEA-induced NF-κB p65 and IκBα phosphorylation were inhibited by corynoline. Furthermore, SIRT1, Nrf2, and HO-1 expression were increased by corynoline. In addition, the protective effects of corynoline against liver injury were reversed by the SIRT1 inhibitor EX-527. Taken together, corynoline protected against ZEA-induced liver injury by activating the SIRT1/Nrf2 signaling pathway.

Topics: Chemical and Drug Induced Liver Injury, Chronic; Humans; Liver; NF-E2-Related Factor 2; NF-kappa B; Signal Transduction; Sirtuin 1; Zearalenone

Zearalenone (ZEA) is a mycotoxin commonly found in cereals and feedstuffs, which can induce oxidative stress and inflammation to cause liver damage in humans and animals. Betulinic acid (BA) is extracted from pentacyclic triterpenoids of many natural plants and has anti-inflammatory, and anti-oxidation biological activities in many studies. However, the protective effect of BA on liver injury induced by ZEA has not been reported. Therefore, this study aims to explore the protective effect of BA on ZEA-induced liver injury and its possible mechanism. In the mice experiment, ZEA exposure increased the liver index and caused histopathological impairment, oxidative damage, hepatic inflammatory responses, and increased hepatocyte apoptosis. However, when combined with BA, it could inhibit the production of ROS, up-regulate the proteins expression of Nrf2 and HO-1 and down-regulate the expression of Keap1, and alleviate oxidative damage and inflammation in the liver of mice. In addition, BA could alleviate ZEA-induced apoptosis and liver injury in mice by inhibiting the endoplasmic reticulum stress (ERS) and MAPK signaling pathways. In conclusion, this study revealed the protective effect of BA on the hepatotoxicity of ZEA for the first time, providing a new perspective for the development of ZEA antidote and the application of BA.

Topics: Animals; Apoptosis; Betulinic Acid; Chemical and Drug Induced Liver Injury, Chronic; Endoplasmic Reticulum Stress; Humans; Inflammation; Kelch-Like ECH-Associated Protein 1; Mice; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction; Zearalenone