EFFECT OF S-ADENOSYLMETHIONINE ON HEPATIC AND METABOLIC DISORDERS IN GUINEA PIGS WITH NONALCOHOLIC STEATOHEPATITIS

Abstract

Objective: S-adenosylmethionine (SAM) has antioxidant and anti-inflammatory actions and hepatoprotective potential. In this study, the therapeutic effectiveness of SAM was investigated in high-fat/cholesterol diet (HFCD)-induced non-alcoholic steatohepatitis (NASH).Material and Methods: In this study, guinea pigs were fed a HFCD for ten weeks to induce NASH. SAM (50 mg/kg, i.p.) was administered to the animals during the last four weeks of the 10-week HFCD regimen. Hepatic damage markers, lipid levels (total cholesterol and triglyceride), inflammatory cytokines (tu mour necrosis-α and interleukin-6) levels, and insulin resistance (HOMA-IR) were determined in the serum. Moreover, hepatic lip ids, SAM and cytochrome p450-2E1 (CYP2E1) levels, prooxidant parameters (reactive oxygen species, lipid peroxides and protein carbonyls) and antioxidant parameters (glutathione levels and antioxidant activity) together with fibrosis indicators (α-smooth muscle actin and transforming growth factor-β1 protein expres sions and hydroxyproline levels) were investigated in the liver. Steatosis, inflammation, and fibrosis scores were also detected histopathologically.Result: SAM treatment diminished the increase in hepatic damage markers, inflammatory cytokine levels, and HOMA-IR levels in the serum of guinea pigs with HFCD-induced NASH. Elevated levels of hepatic triglyceride and CYP2E1 and fibrosis indicators were also detected to decrease due to SAM treatment. This treatment reduced the decrease in SAM levels, disturbance in the prooxidant and antioxidant balance, and diminished the increases in steatosis, inflammation, and fibrosis scores in the liver of guinea pigs fed the HFCD diet.Conclusion: These results indicate that SAM may be effective in HFCD-induced NASH as a therapeutic agent by decreasing lipogenesis, oxidative stress, inflammation, and fibrosis.

Keywords

• s-adenosylmethionine
• nonalcoholic steatohepatitis
• high fat/cholesterol diet
• oxidative stress
• inflammatory cytokines
• guinea pigs