Tyrosol Attenuates High Fat Diet-Induced Hepatic Oxidative Stress: Potential Involvement of Cystathionine β-Synthase and Cystathionine γ-Lyase.

Abstract

The Mediterranean diet is known for its cardioprotective effects. Recently, its protective qualities have also been reported in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress is one of the important factors responsible for the development and progression of NAFLD. Hydrogen sulfide (H2S), a multifaceted gasotransmitter, has emerged as a potential therapeutic target in NAFLD. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are major enzymes responsible for endogenous H2S synthesis. Since oxidative stress contributes to NAFLD pathogenesis, the objective of this study was to investigate the effect of tyrosol, a major compound in olive oil and white wine, on high fat diet-induced hepatic oxidative stress and the mechanisms involved. Mice (C57BL/6) were fed for 5weeks with a control diet (10% kcal fat), a high fat diet (60% kcal fat, HFD) or a HFD supplemented with tyrosol. High fat diet feeding induced hepatic oxidative stress, as indicated by the significant increase in lipid peroxidation and NADPH oxidase activity. Tyrosol supplementation significantly increased hepatic CBS and CSE expression and H2S synthesis in high fat diet-fed mice. Such effects were associated with the attenuation of high fat diet-induced hepatic lipid peroxidation and the restoration of the redox equilibrium of the antioxidant glutathione. Tyrosol also inhibited palmitic acid-induced oxidative stress in hepatocytes (HepG2 cells). These results suggest that the antioxidant properties of tyrosol may be mediated through functional changes in CBS and CSE activity, which might contribute to the hepatoprotective effect of the Mediterranean diet.