TRIGLYCERIDE DISPOSITION IN ISOLATED HEPATOCYTES AFTER TREATMENT WITHHYDRAZINE

Treatment of animals with hydrazine causes the accumulation of triglyc erides in the liver but the mechanism remains unclear. Therefore, the effect of hydrazine on hepatic triglyceride synthesis and subsequent t ransport was studied in a hepatocyte model, in vitro in order to isola te liver cells from extrahepatic influences. Hepatocytes were isolated and either incubated in suspension with [C-14]palmitate in the presen ce of hydrazine (2-12 mM) or pre-incubated with [C-14]palmitate, washe d free of the fatty acid and then incubated with hydrazine (2-12 mM). Hydrazine resulted in a significant reduction in the incorporation of [C-14]palmitate into triglycerides and reduction in the transportation of triglycerides out of cells. When [C-14]palmitate was in the incuba tion medium, ATP levels were reduced by lower concentrations of hydraz ine than have previously been reported. None of the concentrations of hydrazine used affected cell membrane integrity (viability) as measure d by LDH leakage. The (CO2)-C-14 produced by the beta-oxidation of [C- 14]palmitate was also measured in short term incubations (30 min) carr ied out in sealed vessels. There was a dose dependent increase in (CO2 )-C-14 produced by very low concentrations of hydrazine (0.01-0.1 mM) after which the effect was maximal and concentrations above 8 mM hydra zine decreased (CO2)-C-14 production. The data suggest that the inhibi tion of transportation of triglycerides out of cells by hydrazine may have a more important role in the accumulation of triglycerides in the liver than has been previously recognised. However, the model was not able to mimic the accumulation of triglycerides in hepatocytes seen i n vivo. (C) 1997 Elsevier Science Ireland Ltd.