N,N'-diacetylcystine ameliorates inflammation in experimental non-alcoholic steatohepatitis by regulating nuclear transcription factor kappa B activation

Fugen Wang; Shourong Liu; Rangxiao Zhuang; Jianfeng Bao; Yiqin Shen; Jianjun Xi; Jingjing Sun; Hongying Fang

N,N'-diacetylcystine ameliorates inflammation in experimental non-alcoholic steatohepatitis by regulating nuclear transcription factor kappa B activation

Int J Clin Exp Pathol. 2018 Nov 1;11(11):5351-5358. eCollection 2018.

Authors

Fugen Wang¹, Shourong Liu¹, Rangxiao Zhuang¹, Jianfeng Bao¹, Yiqin Shen¹, Jianjun Xi¹, Jingjing Sun¹, Hongying Fang¹

Affiliation

¹ Xixi Hospital of Hangzhou Affiliated to Zhejiang University of Traditional Chinese Medicine Hangzhou, Zhejiang, People's Republic of China.

PMID: 31949616
PMCID: PMC6963052

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide that has been continuously increasing recently. NAFLD embraces a spectrum of liver histological alterations, ranging from simple steatosis (NAFL) to severe non-alcoholic steatohepatitis (NASH), that is characterized by fat accumulation, lobular inflammation, and ballooning degeneration in the hepatocytes in the absence of alcohol abuse. The innate immune system has an important role in NASH pathogenesis. Among the components of innate immunity, the nuclear factor kappa B (NF-κB) has been closely associated with NASH. N,N'-diacetylcystine (DiNAC), the disulfide dimer of N-acetylcysteine (NAC), is a potent modulator of the immune system. Previous research has confirmed that DiNAC has beneficial effects in liver injury. In this study, we aimed to investigate the effects of DiNAC on high fat diet (HFD)-induced NASH in rats. Male Sprague-Dawley rats were fed with HFD to produce the NASH model and treated with or without DiNAC for 8 weeks. We assessed serum levels of alanine-aminotransferase (ALT), aspartate aminotransferase (AST), inflammatory cytokines, liver histology, and the expression of NF-κB genes in the liver. The results showed that the levels of ALT and AST were significantly increased in the HFD rat model. DiNAC treatment also resulted in a statistically significant reduction of the levels of ALT and AST. Hematoxylin and eosin (H&E) staining revealed that DiNAC alleviated histological injury. Moreover, DiNAC strongly reduced the generation of inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β), through NF-κB downregulation. Taken together, these results indicate that DiNAC treatment effectively delayed the progression of NASH by suppressing the expression of NF-κB mRNA in the liver. Our data suggest that DiNAC protects liver injury in HFD-treated NASH rats, which might be a promising drug for the treatment of NASH.

Keywords: N,N’-diacetylcystine; non-alcoholic steatohepatitis; nuclear transcription factor kappa B.