Astaxanthin inhibits alcohol-induced inflammation and oxidative stress in macrophages in a Sirtuin 1-dependent manner

Abstract Objectives Alcohol induces inflammation and oxidative stress, causing cell damages. We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, exerts anti-inflammatory and antioxidant properties in macrophages exposed to inflammatory insults. In this study, we investigated whether ASTX can inhibit alcohol-induced inflammation and oxidative stress in macrophages with the elucidation of mechanisms. Methods RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDM) were treated with 80 mM ethanol in the presence or absence of 25 μM of ASTX for 72 h. Subsequently, the expression of genes related to inflammation and oxidative stress, cellular reactive oxygen species (ROS) accumulation, cellular NAD+ level, and SIRT1 activity were measured. In addition, RAW 264.7 macrophages were treated with sirtinol or resveratrol, which are known inhibitor or activator of SIRT1 activity, respectively, to determine the contribution of SIRT1 to the inhibitory effect of ASTX on inflammation and oxidative stress in macrophages exposed to ethanol. Results Ethanol increased mRNA expression of interleukin (Il)-6, Il-1b, and tumor necrosis factor α with a concomitant increase in nuclear translocation of nuclear factor κB, which was abolished by ASTX. Importantly, ethanol significantly decreased SIRT1 activity and cellular NAD+ level, but ASTX markedly attenuated the decreases in RAW 264.7 macrophages. Sirtinol increased the expression of pro-inflammatory genes in ethanol-induced RAW 264.7 macrophages. In contrast, resveratrol decreased pro-inflammatory gene expression. Conclusions ASTX showed anti-inflammatory and antioxidant properties by inhibiting decreases in SIRT1 expression and cellular NAD+ level in ethanol-treated macrophages. Therefore, ASTX may be used for the prevention of alcohol-induced cell damages.