Orexin-A Improves Hepatic Injury Following Renal Ischemia Reperfusion in Rats

Orexins are novel neuropeptides that are localized in neurons in the lateral hypothalamus. They are implicated in a wide variety of physiological functions. Orexin peptides and receptors are found in many peripheral organs such as kidneys. It has been demonstrated that exogenous orexin-A can induce protective effects against ischemia–reperfusion injury in many organs. The goal of this study was to determine the effect of orexin-A on the hepatic dysfunction and histological damage induced by renal ischemia/ reperfusion at an early stage. Pentobarbital anaesthetized rats were prepared for measuring renal functional variables. Ischemia was induced by bilateral renal artery clamping for 30 min followed by a 1 h reperfusion period. In orexin-treated rats, it was infused at 500 pmol·kg−1·min−1 (i.v.) from the beginning of pre-ischemic (pretreatment) clearance period. The liver was examined using light microscopy. The renal ischemic challenge resulted in hepatic functional and histological damages, which were associated with decreased creatinine clearance during the reperfusion period. In orexin-treated rats, the functional and histological damages to the liver were improved along with the decrease in creatinine clearance being smaller than those of the non-treated rats. Orexin-A exhibited an ameliorative effect against renal ischemia/reperfusion-induced lesions in the liver.