Effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor, on tissue carnitine and lipid levels in rats

MET-88, 3-(2,2,2-trimethylhydrazinium) propionate, suppresses carnitine syn thesis by inhibiting (gamma-butyrobetaine hydroxylase. The purpose of this study was to clarify the effects of suppression of carnitine synthesis on c arnitine and lipid contents in tissues. MET-88 (50, 100, 200 or 400 mg/kg/d ) was administered orally to male SD rats for 10, 30 or 60 d. Total carniti ne and lipid (triglycerides, non-esterified fatty acids) contents were meas ured in heart and liver. In both tissues, treatment with MET-88 dose-depend ently decreased total clarnitine levels, and the reduction reached the plat eau state after 30d at each dose, MET-88 had no effect on lipid content in the heart, but increased the lipid content in the liver at the highest dose s. Treatment with MET-88 at 400 mg/kg for 60 d resulted in no pathologic fi ndings in the histological study; and also had no effect on parameters of l iver function such as glutamic-oxaloacetic transaminase and glutamic-pyruvi c transaminase as judged from the results of blood biochemical analysis. We concluded that long-term treatment with MET-88 decreased the carnitine c ontent to a constant level in both heart and liver, but had no effect on li pid contents in the heart, although it affected lipid metabolism in the liv er.