Combination effect of melatonin and dexamethasone on liver ischemia/reperfusion injury

Liver failure following ischemia-reperfusion (I/R) injury is a major concern in liver surgery. The purpose of this study was to evaluate combination pretreatment with melatonin (MEL) and dexamethasone (DEX) on liver I/R model. Male Wistar rats (n = 60) were assigned to 5 groups of 12 animals each: (1) Sham: laparotomy without I/R; (2) I/R: hepatic I/R; (3) I/R+MEL: hepatic I/R+melatonin injected intraperitoneally (20 mg/kg); (4) I/R+DEX: hepatic I/R+ dexamethasone injected intravenously (10 mg/kg); (5) I/R+MEL+DEX: hepatic I/R+ melatonin injected intraperitoneally+dexamethasone injected intravenously. The liver was subjected to ischemia by clamping the portal triad for 30 minutes and then reperfused for 6 hours after ischemia by removing the clamps.

The levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) decreased after hepatic I/R in all groups. Levels of GPx and SOD were higher in I/R+MEL+DEX group compared to I/R, I/R+MEL and I/R+DEX groups and they were significantly higher in I/R+MEL group compared to I/R and I/R+DEX groups (p < 0.05). Levels of ALT, AST, TNF-α, hepatic tissue malondialdehyde (MDA), liver injury index, and apoptotic index increased after hepatic I/R. Levels of ALT, AST, tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group compared to those in I/R, I/R+MEL and I/R+DEX groups, and in I/R+MEL they were significantly lower than in I/R+DEX group (p < 0.05). TNF-α level was lower in I/R+MEL+DEX group compared to other groups and it was significantly lower in I/R+DEX group than in I/R+MEL and I/R groups (p < 0.05).

Combination therapy with melatonin and dexamethasone had better results in decreasing the liver injury compared to when each of them was administered alone (Tab. 3, Ref. 58).