β-Carotene Protects Mice against Lipopolysaccharide and D-Galactosamine Induced Acute Liver Injury via Regulation of NF-KB, MAPK, and Nrf2 Signaling

Acute liver injury (ALI), posing a serious threaten to our life, has emerged as a public health issue around the world. beta-carotene has plenty of pharmacologic effects, such as anti-inflammatory, antioxidant, and antitumor activities. In this study, we focused on studying the protective role and potential molecular mechanisms of beta-carotene against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced ALI. Our results indicated that beta-carotene pretreatment effectively hindered abnormal changes induced by LPS/ D-GalN in liver histopathology. Meanwhile, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were downgraded with beta-carotene pretreatment. beta-carotene pretreatment also decreased malondialdehyde content and myeloperoxidase activity, increased glutathione peroxidase and superoxide dismutase levels, and reduced the levels of tumor necrosis factor-a (TNF-alpha) and interleukin 6 (IL-6) in liver tissues. Further investigations found that beta-carotene mediated multiple signaling pathways in LPS/D-GalN-induced ALI, inhibiting NF-kappa B and MAPK signaling and upregulating the expression of Nrf2 and HO-1 proteins. All findings indicate that beta-carotene appears to protect mice against LPS/D-GalN induced ALI by reducing oxidative stress and inflammation, possibly via regulating NF-kappa B, MAPK, and Nrf2 signaling.