Protective effects of benfotiamine on irisin activity in methotrexate-induced liver injury in rats

Methotrexate (MTX) causes hepatotoxicity by producing oxidative stress. Benfotiamine and irisin have protective effects against oxidative stress. The aim of this study was to investigate the changes in irisin activity in the liver as a result of toxicity produced by MTX and the protective role of benfotiamine in the hepatotoxicity.

Rats were divided into 4 groups as follows: control, benfotiamine (50 mg/kg, oral gavage (o.g.), for 14 days), MTX (MTX 20 mg/kg intraperitoneally (i.p.) on day 1), MTX + benfotiamine (MTX 20 mg/kg (i.p.) on day 1, then 50 mg/kg (o.g.) benfotiamine for 14 days). Liver tissue was used to examine histopathological and immunohistochemical changes. Serum was used to look for oxidative stress markers (total antioxidant status (TAS) and total oxidant status (TOS)).

Administration of MTX caused a significant TOS increase and TAS decrease in the serum as compared to the control group. Immunohistochemically, irisin was significantly increased in immunoreactivity in the MTX group as compared to the control group (p < 0.05). Significant histopathological improvement and decrease in serum TOS levels were observed in the MTX + benfotiamine group compared to the MTX group (p < 0.05). In addition, an increase in TAS level and a decrease in irisin immunoreactivity were observed but they were not statistically significant (p > 0.05).

Our results showed that MTX caused an increase in the activity of irisin after producing toxicity in the liver. In addition, we found that benfotiamine was effective in preventing damage caused by MTX in the liver.