Alpha-lipoic acid exerts a liver-protective effect in acute liver injury rats

作者：Tanaka Yoshito; Kaibori Masaki; Miki Hirokazu; Nakatake Richi; Tokuhara Katsuji; Nishizawa Mikio; Okumura Tadayoshi^*; Kwon A Hon

来源：Journal of Surgical Research, 2015, 193(2): 675-683.

DOI：10.1016/j.jss.2014.08.057

• Tumor necrosis factor-alpha
• Inducible nitric oxide synthase
• Interleukin-10
• Nuclear factor-kappa B
• D-galactosamine and lipopolysaccharide
• Acute liver injury

Background: Recent evidence indicates that alpha-lipoic acid (alpha-LA) has a variety of liver-protective effects through the suppression of inflammatory mediators including tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS). However, there are few reports that alpha-LA markedly enhanced the survival rate in animal models of liver injury with more than 90% death. The aim of this study was to investigate the beneficial effects of alpha-LA in a rat model of acute liver injury and to clarify the mechanisms of alpha-LA action.
Methods: Rats were treated with D-galactosamine and lipopolysaccharide (GalN and LPS) to induce acute liver injury. alpha-LA (100 mg/kg) was administered intraperitoneally 1 h before GalN and LPS injection. Inflammatory mediators including TNF-alpha and iNOS were analyzed.
Results: A single injection of alpha-LA improved the survival rate by more than 80%. alpha-LA prevented serum transaminase increases, histopathologic changes, and apoptosis in the liver. In the serum, alpha-LA decreased TNF-alpha production and increased interleukin (IL)-10 production. In the liver, alpha-LA reduced TNF-alpha and IL-6 messenger RNA (mRNA) but enhanced IL-10 mRNA. alpha-LA decreased the expression of iNOS mRNA and its antisense transcript, leading to the reduction of iNOS protein expression and resulting in the inhibition of nitric oxide production. An electrophoretic mobility shift assay revealed that alpha-LA reduced the activation of nuclear factor-kappa B induced by GalN and LPS.
Conclusions: alpha-LA inhibited the induction of inflammatory mediators, such as TNF-alpha and iNOS, in part through the inhibition of nuclear factor-kappa B activation and enhanced the induction of IL-10. alpha-LA may have therapeutic potential for use in the prevention of acute liver injury.

• 出版日期2015-2