Exercise-Induced Increase in Serum Irisin Levels is Associated with Antioxidant Effects of Silymarin in Dexamethasone- Induced NAFLD.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no specific treatment. We examined the effects of silymarin, exercise, and their combination on the serum levels of oxidant/antioxidant markers, as well as irisin-a myokine secreted by muscles during exercise-in dexamethasone-induced NAFLD in adult male rats. Methods: In this experimental animal study, forty-two male Wistar rats were randomly grouped into control (normal saline), NAFLD (dexamethasone injection at 10 mg/kg/day, s.c. for 7 days to induce NAFLD), NAFLD + exercise training (continuous exercise training 5 days/week for 8 weeks), NAFLD + silymarin (1 mg/kg/day, orally for 8 weeks), NAFLD + exercise training + silymarin, and NAFLD + pioglitazone (positive control, 1 mg/kg/day, orally for 8 weeks) groups (n = 7 for each). The serum levels of oxidant markers, malondialdehyde (MDA); antioxidant markers, superoxide dismutase (SOD); total antioxidant capacity (TAC); and irisin were determined using specific ELISA kits. Results: Oxidant markers, such as MDA, were significantly enhanced while antioxidant markers, such as SOD and TAC, as well as serum levels of irisin, were significantly diminished in rats with NAFLD compared to controls. Combining silymarin and 8-week continuous training exercise resulted in significant restoration of serum levels of MDA, TAC, and irisin to control values. While combined treatment had a significant impact on oxidant/antioxidant status in NAFLD rats, it was not more effective than either treatment alone. However, it was observed that the serum level of irisin increased more in combination therapy. Conclusions: Our findings suggest that combination treatment with silymarin and exercise may have a protective effect against NAFLD, partly by reducing oxidative stress and increasing serum levels of irisin.