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

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.