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

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 were treated with 80 mM ethanol in the presence or absence of 25 AM of ASTX for 72 h. Subsequently, the expression of genes related to inflammation and oxidative stress, cellular reactive oxygen species accumulation, cellular NAD(+) level and sirtuin 1 (SIRTI) activity were measured. In addition, RAW 264.7 macrophages were treated with sirtinol or resveratrol, which are known inhibitors or activators of SIRTI activity, respectively, to determine the contribution of SIRTI 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 alpha with a concomitant increase in nuclear translocation of nuclear factor kappa B, 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 proinflammatoiy genes in ethanol-induced RAW 264.7 macrophages. In contrast, resveratrol decreased proinflammatory 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, MIX may be used for the prevention of alcohol-induced cell damages. (C) 2020 Elsevier Inc. All rights reserved.