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

Abstract

MET-88, 3-(2,2,2-trimethylhydrazinium) propionate, suppresses carnitine synthesis by inhibiting (γ-butyrobetaine hydroxylase. The purpose of this study was to clarify the effects of suppression of carnitine synthesis on carnitine 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 carnitine and lipid (triglycerides, non-esterified fatty acids) contents were measured in heart and liver. In both tissues, treatment with MET-88 dose-dependently decreased total carnitine levels, and the reduction reached the plateau state after 30 d 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 doses. Treatment with MET-88 at 400 mg/kg for 60 d resulted in no pathologic findings in the histological study, and also had no effect on parameters of liver function such as glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase as judged from the results of blood biochemical analysis. We concluded that long-term treatment with MET-88 decreased the carnitine content to a constant level in both heart and liver, but had no effect on lipid contents in the heart, although it affected lipid metabolism in the liver.