chicoric-acid and Chemical-and-Drug-Induced-Liver-Injury

Chicoric acid is polyphenol of natural plant and has a variety of bioactivity. Caused by various kinds of stimulating factors, acute liver injury has high fatality rate. The effect of chicoric acid in acute liver injury induced by Lipopolysaccharide (LPS) and d-galactosamine (d-GalN) was investigated in this study. The results showed that CA decreased the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and reduced the mortality induced by LPS/d-GalN. CA can restrain mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) to alleviate inflammation. Meanwhile, the results indicated CA can active nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway with increasing the level of AMP-activated protein kinase (AMPK). And with the treatment of CA, protein levels of autophagy genes were obvious improved. The results of experiments indicate that CA has protective effect in liver injury, and the activation of AMPK and autophagy may make sense.

Topics: Alanine Transaminase; AMP-Activated Protein Kinase Kinases; Animals; Aspartate Aminotransferases; Autophagy; Caffeic Acids; Chemical and Drug Induced Liver Injury; Galactosamine; Gene Expression Regulation; Hep G2 Cells; Humans; Inflammation; Lipopolysaccharides; Liver; Mice; Mitogen-Activated Protein Kinase Kinases; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Protein Kinases; Succinates

Chicoric acid (CA) is a natural antioxidant with promising hepatoprotective activity. We investigated the potential of CA to prevent methotrexate (MTX) hepatotoxicity, pointing to the role of Nrf2/HO-1 signaling and PPARγ. Rats received CA for 15 days and were then injected with MTX at day 16. Blood and tissue samples were collected for analysis at day 19. CA ameliorated liver function markers and mitigated histological alterations in MTX-induced rats. Pre-treatment with CA suppressed reactive oxygen species and lipid peroxidation and enhanced antioxidants in MTX-induced rats. Moreover, CA upregulated hepatic Nrf2, HO-1, NQO-1, and PPARγ, and attenuated inflammation. Consequently, CA inhibited apoptosis by increasing Bcl-2 expression and suppressing Bax, cytochrome c, and caspase-3 in MTX-administered rats. In conclusion, CA prevented oxidative stress, inflammation, and liver injury induced by MTX by activating Nrf2 /HO-1 signaling and PPARγ.

Topics: Animals; Antioxidants; Caffeic Acids; Chemical and Drug Induced Liver Injury; Inflammation; Liver; Methotrexate; NF-E2-Related Factor 2; Oxidative Stress; PPAR gamma; Rats; Rats, Wistar; Succinates; Up-Regulation