Prevention of galactosamine-induced liver cell necrosis by uridine.

Abstract

The administration of galactosamine to rats produces dose-dependent liver cell injury. A relatively low dose of galactosamine (200 mg/kg) causes a marked fall in UTP with an accompanying inhibition of RNA and protein synthesis. Uridine will reverse the UTP deficiency and the inhibition of RNA and protein synthesis at any time. The administration of a larger dose of galactosamine (400 mg/kg) produces liver cell necrosis within 12 hours. Although the effects on macromolecular synthesis are very similar with the two doses, cell necrosis distinguishes the reaction of the liver to the larger dose from that to the lower. Uridine will also prevent the development of liver cell necrosis, even if given as late as 3 hours after the galactosamine. This was shown by examination of the changes in serum glutamic oxalocetic transaminase levels and by examination of the histologic changes in the livers. Other purines do not have this protective effect; adenine is unable to prevent liver cell necrosis. As the known biochemical effects of the two doses of galactosamine are very similar during the first 3 hours, the protective effect of uridine seems to imply the existence of an as yet unknown lesion distinguishing the reaction of the liver cell to the larger dose of galactosamine. Uridine must prevent the appearance of this lesion or reverse its development.