Detrimental effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a mutagenic agent, on mitochondrial respiration among various rat tissues.
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.
Sugiyama
S
S
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Takasawa
M
M
Hayakawa
M
M
Esumi
H
H
Ozawa
T
T
D000375:Aging; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D016658:Psoas Muscles / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
D007093:Imidazoles; D009097:Multienzyme Complexes; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III