Inhibition of alcohol-induced inflammation and oxidative stress by astaxanthin is mediated by its opposite actions in the regulation of sirtuin 1 and histone deacetylase 4 in macrophages

We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, repressed ethanol-induced inflammation and oxidative stress in macrophages. explored the role of sirtuin 1 (SIRT1) histone deacetylase 4 (HDAC4) inhibitory effect ASTX on macrophages exposed to ethanol. Ethanol decreased mRNA protein SIRT1 while increasing those HDAC4, which was attenuated by RAW 264.7 mouse bone marrow-derived (BMDMs). Inhibition expression or activity augmented Hdac4 expression, but activation elicited opposite effect. Consistently, knockdown increased Sirt1 with decreases inflammatory gene its overexpression resulted effects. Furthermore, BMDMs from mice macrophage specific-deletion (Hdac4MKO) showed significant genes ROS accumulation an increase expression. Macrophage specific deletion abolished changes for mitochondrial biogenesis glycolysis respiration, ATP production, proton leak, maximal respiration spare respiratory capacity, all were The alterations abrogated Hdac4MKO BMDMs. In conclusion, anti-inflammatory antioxidant properties ethanol-treated may be mediated, at least partly, HDAC4 empower counteract HDAC4.