Beneficial effects of diacerein on adipokines and pro-inflammatory cytokines involved in diet-induced nonalcoholic steatohepatitis in rats
Keywords:Adipokines, Diacerein, Non-alcoholic steatohepatitis, Pro-inflammatory cytokines, Rat
Background: Non-alcoholic steatohepatitis (NASH) is considered as a progressive liver disease, so effective therapies are needed to ameliorate hepatic steatosis, inflammation and fibrosis, and to prevent the progression to cirrhosis and hepatocellular carcinoma. Diacerein is an anti-inflammatory drug that inhibits the synthesis and activity of pro-inflammatory cytokines. The present study was designed to investigate the effect of diacerein on pro-inflammatory cytokines as well as adipokines involved in diet-induced NASH rat model.
Methods: Thirty-two adult male rats were divided into four groups: control, diacerein-treated, NASH-untreated and NASH+diacerein-treated groups. NASH was induced by feeding rats with high-fat and high-cholesterol diet for 12 weeks. Body weight, liver weight, fasting blood glucose and insulin levels for estimation of insulin resistance, blood lipids, alanine transaminase, and aspartate aminotransferase were evaluated. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), adiponectin, visfatin and leptin were also detected. Histopathological examination of liver sections was performed.
Results: Diacerein significantly reduced liver weight, fasting blood glucose, insulin level, transaminases and ameliorates insulin resistance with favourable effects on blood lipids. These results were accompanied with a significant reduction in serum levels of TNF-α, IL-1β, IL-6, and visfatin, while, adiponectin was significantly increased and leptin was insignificantly affected. Liver sections revealed that diacerein reduced steatosis and lobular inflammatory grades.
Conclusions: These data suggest that diacerein administration may have a potential usefulness in the prevention of NASH as a possible result of inhibition of pro-inflammatory cytokines and the beneficial effects on adipokines especially adiponectin and visfatin.
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