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 μM 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 (SIRT1) activity were measured. In addition, RAW 264.7 macrophages were treated with sirtinol or resveratrol, which are known inhibitors or activators 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 proinflammatory 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, ASTX may be used for the prevention of alcohol-induced cell damages.

中文翻译：

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虾青素以sirtuin 1依赖性方式抑制巨噬细胞中酒精诱导的炎症和氧化应激。

目标

酒精会引起炎症和氧化应激，从而导致细胞损伤。我们以前证明了虾青素（叶黄素类胡萝卜素）在暴露于炎性损伤的巨噬细胞中具有抗炎和抗氧化特性。在这项研究中，我们调查了ASTX是否可以通过阐明机理来抑制巨噬细胞中酒精诱导的炎症和氧化应激。

方法

在存在或不存在25μMASTX的情况下，用80 mM乙醇处理RAW 264.7巨噬细胞和小鼠骨髓衍生的巨噬细胞72小时。随后，测量与炎症和氧化应激，细胞活性氧累积，细胞NAD ⁺水平和Sirtuin 1（SIRT1）活性相关的基因的表达。此外，分别用已知的SIRT1活性抑制剂或西敏醇或白藜芦醇处理RAW 264.7巨噬细胞，以确定SIRT1对ASTX抑制乙醇暴露的巨噬细胞炎症和氧化应激的抑制作用。

结果

乙醇可增加白介素（Il）-6，II-1b和肿瘤坏死因子α的mRNA表达，并伴随核因子κB的核易位增加，而这被ASTX取消。重要的是，乙醇显着降低了SIRT1活性和细胞NAD ⁺水平，但ASTX明显减弱了RAW 264.7巨噬细胞的下降。Sirtinol增加了乙醇诱导的RAW 264.7巨噬细胞中促炎基因的表达。相反，白藜芦醇降低了促炎基因的表达。

结论

ASTX通过抑制乙醇处理的巨噬细胞中SIRT1表达和细胞NAD ⁺含量的降低而显示出抗炎和抗氧化特性。因此，ASTX可用于预防酒精诱导的细胞损伤。