Beta-alanine protection against hypoxic liver injury in the rat

Abstract

Liver hypoxia still represents an important cause of liver injury during shock and liver transplantation. We have investigated the protective effects of β-alanine against hypoxic injury using isolated perfused rat livers and isolated rat hepatocyte suspensions. Perfusion with hypoxic Krebs–Henseleit buffer increased liver weight and caused a progressive release of lactate dehydrogenase (LDH) in the effluent perfusate. The addition of 5 mmol/l β-alanine to the perfusion buffer completely prevented both weight increase and LDH leakage. These findings were confirmed by histological examinations showing that β-alanine blocked the staining by trypan blue of either liver parenchymal and sinusoidal cells. Studies performed in isolated hepatocytes revealed that β-alanine exerted its protective effects by interfering with Na + accumulation induced by hypoxia. The addition of γ-amino-butyric acid, which interfered with β-alanine uptake by the hepatocytes or of Na +/H + ionophore monensin, reverted β-alanine protection in either hepatocyte suspensions or isolated perfused livers. We also observed that liver receiving β-alanine were also protected against LDH leakage and weight increase caused by the perfusion with an hyposmotic (205 mosm) hypoxic buffer obtained by decreasing NaCl content from 118 to 60 mmol/l. This latter effect was not reverted by blocking K + efflux from hepatocyte with BaCl 2 (1mmol/l). Altogether these results indicated that β-alanine protected against hypoxic liver injury by preventing Na + overload and by increasing liver resistance to osmotic stress consequent to the impairment of ion homeostasis during hypoxia.