Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress - PubMed (original) (raw)

Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress

Alireza Rezazadeh et al. J Biomed Sci. 2012.

Abstract

Background: Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. It has been suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. The aim of present study was to determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C could improve the biochemical and histological abnormalities associated with diet-induced NASH in rats.

Methods: NASH was induced in male N-Mary rats by feeding a methionine - choline deficient (MCD) diet. The rats were fed either normal chow or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly divided into four groups of six: the NASH group that received MCD diet, the EUK-8 group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK-8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage for eight weeks.

Results: Treatment of MCD-fed rats with salens reduced the sera aminotransferases, cholesterol, low density lipoprotein contents, the extent of lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis, ballooning degeneration and inflammation in liver of MCD-fed rats.

Conclusion: Antioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced biochemical and histological abnormalities, pointing out that antioxidant strategy could be beneficial in treatment of NASH.

© 2012 Rezazadeh et al; licensee BioMed Central Ltd.

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Figures

Figure 1

Figure 1

Chemical structures of the Mn-salen complexes EUK-8 and EUK-134.

Figure 2

Figure 2

Histological evaluation of rats' livers. Photographs of tissues after Hematoxylin-eosin (A-E) or Masson trichrome staining (F). Original magnifications ×100. (A) Normal liver histology of a rat fed the standard diet. (B) MCD-fed diet (NASH group) showing ballooning degeneration, pericentral macrovesicular steatosis and lobular inflammation. (C) group MCD-fed diet + EUK-8 showing normal architecture with neither steatosis nor inflammation. (D) group MCD-fed diet + EUK-134 showing normal architecture with neither steatosis nor inflammation. (E) group MCD-fed diet + Vitamin C showing normal architecture, focal macrovesicular steatosis and no inflammation. No evidences of drug toxicity have been seen in all drug treated MCD-fed group. (F) No significant fibrosis is detected in MCD-fed group. MCD: methionine and choline deficient diet.

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