Effect of 3-(2,2,2-trimethylhydrazinium) propionate, gamma-butyrobetaine hydroxylase inhibitor, on isoproterenol-induced mitochondrial dysfunction.
The present study was designed to investigate whether or not reduction of carnitine content could protect isoproterenol (ISP)-induced myocardial injury using 3-(2,2,2-trimethylhydrazinium) propionate (TMHP), gamma-butyrobetaine hydroxylase inhibitor. Rats were divided into 4 groups; the control group: untreated, the TMHP-1 group: TMHP (100 mg/kg) was administered intraperitoneally, and ISP (10 mg/kg) was administered subcutaneously on the following day, the TMHP-7 group: TMHP (100 mg/kg) for 7 successive days, and ISP (10 mg/kg) on the eighth day, the ISP group: ISP (10 mg/kg) was administered. Rats were cervically dislocated 15 hours after ISP administration, and heart mitochondrial electron-transport activity (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) were measured enzymatically. Activity of succinate-cytochrome c reductase was not affected significantly by ISP, however, NADH-cytochrome c reductase and cytochrome c oxidase were significantly reduced in the ISP and TMHP groups. Administration with TMHP for 7 successive days lessened the reduction of the activities. Mitochondrial electron-transport system plays an important role in cellular energy transduction. These results suggested that mitochondrial dysfunction induced by ISP is related to carnitine-dependent fatty acid metabolism and that TMHP reduces the myocardial injury.
Hanaki
Y
Y
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Ozawa
T
T
D000818:Animals; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008763:Methylhydrazines / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009245:NADH Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D050563:gamma-Butyrobetaine Dioxygenase
D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D006899:Mixed Function Oxygenases; D050563:gamma-Butyrobetaine Dioxygenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D007545:Isoproterenol