Effect of 3-(2,2,2-trimethylhydrazinium) propionate, gamma-butyrobetaine hydroxylase inhibitor, on isoproterenol-induced mitochondrial dysfunction

Res Commun Chem Pathol Pharmacol. 1989 Apr;64(1):157-60.

Abstract

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.

MeSH terms

  • Animals
  • Electron Transport
  • Electron Transport Complex IV / metabolism
  • In Vitro Techniques
  • Isoproterenol / pharmacology*
  • Methylhydrazines / pharmacology*
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / enzymology*
  • Mixed Function Oxygenases / antagonists & inhibitors*
  • NADH Dehydrogenase / metabolism
  • Rats
  • Rats, Inbred Strains
  • gamma-Butyrobetaine Dioxygenase

Substances

  • Methylhydrazines
  • 3-(2,2,2-trimethylhydrazine)propionate
  • Mixed Function Oxygenases
  • gamma-Butyrobetaine Dioxygenase
  • NADH Dehydrogenase
  • Electron Transport Complex IV
  • Isoproterenol