Protective effects of trimetazidine against hepatic warm ischemia/reperfusion injury on rats

Abstract

Non-alcoholic fatty liver disease (NAFLD) is related to insulin resistance, obesity, hyperlipidemia, and oxidative stress. Trimetazidine (TMZ) is an anti-ischemic piperazine derivative. This study aims to investigate the protective effect of the TMZ against warm ischemia-reperfusion (I/R) damage in the liver on an experimental NAFLD model. The blood samples for biochemical analysis and liver tissue for histopathological analysis were collected from rats. A total of 32 Sprague Dawley male rats was divided into four groups. Group 1 (controls, n = 6); rats were fed the standard basal diet for eight weeks and underwent no surgery. Group 2 (sham-operated group n = 6); rats were fed a high-fat diet for eight weeks and underwent laparotomy without warm I/R damage. Group 3 (warm I/R group, n=10); rats were fed a high-fat diet for eight weeks, and warm I/R damage was created. Group 4 (warm I/R+TMZ group (n=10); rats were fed a high-fat diet for eight weeks, and the TMZ (10 mg/kg) was given a single dose by the orogastric way 30 minutes before the warm I/R was created. In Group 4, while the TMZ caused to decrease in levels of oxidative stress markers; MPO (p<0.001), NOX (p<0.001), and Cyt-C (p<0.001) increased the activity of the antioxidant enzyme CAT (p<0.001) as compared to Group 3. There is no significant difference in levels of other oxidant markers, MDA and 8-OHDG in all groups (p>0.05). The hepatocyte cell damage in cell groups related to I/R damage was observed. Against this observation, the TMZ improved dilatation of sinusoids, inflammation, and structural integrity of hepatic plaques in group 4. In conclusion, TMZ could improve the antioxidant defense mechanism upon oxidative damage and increase cells' survival rate by protecting mitochondrial integrity in NAFLD.