Detrimental effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a mutagenic agent, on mitochondrial respiration among various rat tissues

Biochem Mol Biol Int. 1993 Aug;30(5):797-805.

Abstract

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a potent mutagenic agent produced during thermal processing of meats. Since 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine has a similar structure to tetrahydroisoquinoline, a mitochondria toxic compound, we determined whether or not this compound shows detrimental effects on mitochondrial electron transport activities in various rat tissues. Administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 100 mg/kg twice a week for 4 weeks, decreased significantly the activity of complex I in mitochondrial electron transport chain of heart, diaphragm, and psoas major, while it did not affect the activities of complex I in the liver mitochondria. Concerning the activities of complexes II, III, and IV, no significant effects were observed irrespective of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administration. Age-related deterioration of mitochondrial function seems to be a major contributor to age-related decline in cellular function. From our results, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine might act as an accelerator of age-related decline in mitochondrial function.

MeSH terms

  • Aging
  • Animals
  • Diaphragm / drug effects
  • Diaphragm / metabolism
  • Electron Transport / drug effects
  • Electron Transport Complex II
  • Electron Transport Complex III / metabolism
  • Electron Transport Complex IV / metabolism
  • Imidazoles / toxicity*
  • Male
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / metabolism
  • Multienzyme Complexes / metabolism
  • Mutagens / administration & dosage
  • Mutagens / toxicity*
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Oxidoreductases / metabolism
  • Oxygen Consumption / drug effects*
  • Psoas Muscles / drug effects
  • Psoas Muscles / metabolism
  • Rats
  • Rats, Wistar
  • Succinate Dehydrogenase / metabolism

Substances

  • Imidazoles
  • Multienzyme Complexes
  • Mutagens
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Oxidoreductases
  • Electron Transport Complex II
  • Succinate Dehydrogenase
  • NAD(P)H Dehydrogenase (Quinone)
  • Electron Transport Complex IV
  • Electron Transport Complex III