Co-administration of melatonin and dexamethasone attenuates lung tissue injury after liver ischemia/reperfusion

Abstract

Ischemia-reperfusion injury (IRI) is a common and important clinical problem in many different organ systems. Once the blood flow and oxygen supply are reestablished, reperfusion enhances the injury caused by the ischemic period. This phenomenon, known as ischemia/reperfusion (IR) injury, impacts directly on liver viability, especially during transplantation and liver surgery. The purpose of this study was to evaluate combination pretreatment of melatonin (MEL) and dexamethasone (DEX) on liver I/R model of lung injury. Male Wistar rats (n=60) were assigned to 5 groups of 12 animals each: 1: Sham; Laparatomy without I/R 2: I/R; underwent hepatic I/R. 3: I/R+MEL; hepatic I/R+ injected intraperitoneally melatonin (20 mg/kg). 4: I/R+DEX; hepatic I/R+ injected intravenously dexamethasone (10 mg/kg). 5: I/R+MEL+DEX; hepatic I/R+ injected intraperitoneally melatonin + injected intravenously dexamethasone. Liver subjected to ischemia by clamping portal triad for 30 minutes and was reperfused for 6 hours after ischemia by removing the clamps. 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 comparing to I/R, I/R+MEL and I/R+DEX groups significantly(P<0. 05), and they were higher in I/R+MEL group comparing to I/R and I/R+DEX groups but it was not significant. Lung tissue malondialdehyde (MDA), lung injury index, and apoptotic index increased after hepatic I/R. Tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group comparing to I/R, I/R+MEL and I/R+DEX groups significantly(P<0. 05), and in I/R+MEL was lower than I/R+DEX group but it was not significant. Coadministration of melatonin and dexamethasone had better results in decreasing the lung injury after hepatic I/R, comparing to administering each of them alone.