Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver disease. (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis without a relevant alcohol consumption (˂ 20 g/day). It is estimated that NAFLD prevalence in the world ranges from 20 to 30%.It has been recognized as a major cause of liver-related morbidity and mortality. Histological changes of NASH are characterized by steatosis, mixed inflammatory cell infiltration, necrosis and progressive fibrosis, ultimately leading to cirrhosis and end-stage liver disease. A choline deficient (CD) diet induce a comprehensive histological and dysmetabolic phenotype resembling human NAFLD.
Vitamin D has been shown to act as an immunomodulatory, antioxidant, anti-inflammatory, antiapoptotic and anti fibrotic compound in rats. This study was carried out in order to clarify the protective effect of vitamin D supplementations on fatty liver in rats induced by CD diet.
This study was carried out on 5 main groups of adult male albino rats. The first of them is the control group received standard diet with no medications. The 2ndgroup received CD diet for 12 weeks which resulted in development of fatty liver. The 3rdgroup received CD diet + vit D in a dose of (1µ/kg) IP twice a week for 12 weeks. The 4th group received CD diet +vit D in a dose of (5 µ/kg) IP twice a week ) for 12 weeks. The 5thgroup received CD diet + vit D injection in a dose of (10 µ/kg) IP twice a week for 12 weeks.
The parameters used to evaluate the consequences of fatty liver were serum levels of AST activity, ALT activity , albumin and bilirubin. Also serum level of vit D was measured. The body weight, liver weight and liver index were measured. Histopathological examination of the liver by H&E was used to confirm our results and immunohistochemical examination of TGFβ1 in the liver to assess the anti fibrotic effect of vit D was assessed.
The obtained results of this study could be summarized as follow:
- CD diet administration for 12 weeks resulted in fatty liver manifested by a significant increase in the serum level of AST activity , ALT activity ,a decrease in serum 25 (OH) VIT D level ,an increase in liver weight and liver index. The histopathological examination of the liver by H&E showed severe steatosis of hepatocytes and inflammatory cells infiltration. The immunohistochemical examination of TGFβ1 in the liver showed strong positive expression (immunopositivity indicated by brown color).
- On studying the protective effect of vit D administration by (IP) injection in a dose of (1,5,&10 µ/kg) for 12 weeks on the liver functions , serum level of 25(OH) vit D ,liver weight and liver index, there were a significant decrease in the serum level of AST activity, ALT activity , an increase in serum 25 (OH) VIT D level , a decrease in liver weight and liver index. The histopathological examination of the liver by H&E showed moderate hydrobic degeneration of hepatocytes, portal inflammatory cells infiltration ,a slight activation of kupffer cells and slight cytoplasmic vaculization of focal hepatocytes indicating regression of the disease in a dose dependent manner. The immunohistochemical examination of TGFβ1 in the liver showed decrease in the expression of it in a dose dependent manner (decrease in the brown color) indicating the protective role of vit D in regression of the disease.
From the above results we conclude that the pathogenesis of NAFLD is mediated through CD diet and vitamin D has a hepato-protective effect that could be mediated through TGFβ1.
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