Liver
hypoxia still represents an important cause of liver injury during
shock and
liver transplantation. We have investigated the protective effects of
beta-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
beta-alanine to the perfusion
buffer completely prevented both weight increase and LDH leakage. These findings were confirmed by histological examinations showing that
beta-alanine blocked the staining by
trypan blue of either liver parenchymal and sinusoidal cells. Studies performed in isolated hepatocytes revealed that
beta-alanine exerted its protective effects by interfering with Na+ accumulation induced by
hypoxia. The addition of gamma-amino-
butyric acid, which interfered with
beta-alanine uptake by the hepatocytes or of Na+/H+
ionophore monensin, reverted
beta-alanine protection in either hepatocyte
suspensions or isolated perfused livers. We also observed that liver receiving
beta-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
beta-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.