title: Mitochondrials complex I activity is reduced in latent adriamycin-induced cardiomyopathy of rat.
abstract: We previously reported on the use of enzymatic analysis to impair fatty acid metabolism followed by reduced myocardial energy content, leading to severe heart failure in adriamycin (ADR)-treated rats. The aim of this study is to investigate whether impaired myocardial energy metabolism can also be detected by other methods; i.e. measuring mitochondrial complex I activity and myocardial 125I-15-(p-iodophenyl)-3-(R,S)- methylpentadecanoic acid (BMIPP) accumulation in ADR-treated rats. Eight-week-old male Sprague-Dawley rats received 6 intraperitoneal injections of ADR (total 15 mg/kg: group ADR) or saline (control group) over 2 weeks. Left ventricular (LV) ejection fraction was assessed using echocardiography at 3- and 6-weeks after ADR injection (3 weeks and 6 weeks, respectively). Myocardial fatty acid utilization was assessed at 3 weeks and 6 weeks. The myocardial counts of BMIPP were measured after intravenous BMIPP (370 kBq) injection, and 125I counts were measured to calculate the uptake ratio. The enzymatic activity of complex I was assessed by monitoring the oxidation of nicotinamide-adenine-dinucleotide-disodium-salt (NADH). In rats treated with ADR, significant decrease in LV ejection fraction was observed only at 6 weeks compared to control (72.5 vs. 84.5%, p < 0.01). LV ejection fraction at 3 weeks was identical between group ADR and control (81.8 vs. 84.4%). However, at 3 weeks, complex I activity was already reduced significantly in group ADR as compared to control group (p = 0.03), but the reduction in BMIPP accumulation was not (p = 0.15). Our data indicated that reduced complex I activity in a phenomenon occurred in early phase of ADR-induced cardiomyopathy, and it might play an important role in the progression of ADR-induced heart failure.
authors.affiliation: First Department of Internal Medicine, Fukui Medical University, Shimoaizuki, Matsuoka-cho, Fukui, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Ohkura
authors.forename: Jong-Dae
authors.initials: JD
authors.lastname: Lee
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Shimizu
authors.forename: Akira
authors.initials: A
authors.lastname: Nakano
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Uzui
authors.forename: Motosaburo
authors.initials: M
authors.lastname: Horikoshi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Fujibayashi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Yonekura
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001835:Body Weight; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology*; D004452:Echocardiography; D005227:Fatty Acids / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D006339:Heart Rate; D006352:Heart Ventricles / Q000473:pathology; D007462:Iodobenzenes / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D005227:Fatty Acids; D007462:Iodobenzenes; C049338:iodofiltic acid; D009243:NAD; D004317:Doxorubicin; C067799:4-iodophenyl-9-methylpentadecanoic acid; D010100:Oxygen