S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

Drug Des Devel Ther. 2013 Jun 28;7:553-63. doi: 10.2147/DDDT.S43930. Print 2013.

Abstract

S-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor β-1 [TGFβ-1], collagen-1α, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGFβ-1, and collagen-1α. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH.

Keywords: NASH; S-nitroso-N-acetylcysteine; diethylnitrosamine; fibrogenesis; nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / metabolism
  • Acetylcysteine / therapeutic use
  • Animals
  • Fatty Liver / drug therapy*
  • Immunohistochemistry
  • Liver Cirrhosis, Experimental / prevention & control*
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Non-alcoholic Fatty Liver Disease
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley

Substances

  • S-nitroso-N-acetylcysteine
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Acetylcysteine