1182 EXPERIMENTAL MODELS OF MICROVESICULAR FATTY CHANGE IN RAT LIVER

Abstract

An association of microvesicular hepatic fatty change with hyperammonemia and orotic aciduria (OAuria) has been noted in several pediatric conditions, including Reye's syndrome. Experimental OA supplementation produces fatty changes in rat liver. In the present study severe hyperammonemia (2-3 mg%), without OAuria was produced by repeated administration of urease (25 U/kg) for periods up to 24 hrs. The hyperammonemic rats were found to have hyperglycemia (374±21 mg%: controls: 172±6 mg%), elevated plasma FFA (815±62 μEq/1: controls 491±25 μEq/1) and hepatic triglycerides (15.6±1.4 mg/gm: controls: 2.7±0.2 mg/gm) (SEM). Liver sections stained with oil red O showed microvesicular fatty changes. To evaluate the role of OA in the development of fatty changes, conversion of OA to uridine monophosphate (UMP) was blocked with azauridine. Under these conditions fatty changes resulting from urease-induced hyperammonemia were markedly less than those observed without azauridine. It is concluded that increased availability of carbamyl phosphate in hyperammonemia leads to overproduction of OA and that the conversion of increased amounts of OA to UMP rather than OA elevation was an essential prerequisite to the induction of hepatic microvesicular fatty changes.