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 synthesis by inhibiting (gamma-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.
Hayashi
Y
Y
Pharmacology Research Laboratory, Taiho Pharmaceutical Co.. Ltd., Tokushima, Japan. yucky@mail.netwave.or.jp
Muranaka
Y
Y
Kirimoto
T
T
Asaka
N
N
Miyake
H
H
Matsuura
N
N
D000818:Animals; D002331:Carnitine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050563:gamma-Butyrobetaine Dioxygenase
D004791:Enzyme Inhibitors; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D006899:Mixed Function Oxygenases; D050563:gamma-Butyrobetaine Dioxygenase; D002331:Carnitine