An animal model of mitochondrial myopathy: a biochemical and physiological investigation of rats treated in vivo with the NADH-CoQ reductase inhibitor, diphenyleneiodonium.
Chronic administration of the NADH-CoQ reductase inhibitor, diphenyleneiodonium to rats at two dose levels, 1.0 and 1.5 mg/kg per day, caused a 40% and 60% reduction, respectively, in the in vitro rate of NAD-linked respiration by skeletal muscle mitochondria. At the highest dose, muscle fatigue, lactic acidosis and an over-utilization of phosphocreatine was observed in the gastrocnemius muscle during mild stimulation of 1 Hz frequency. The resynthesis of phosphocreatine following muscle stimulation was about 2 fold slower in the treated animal group. At the low dose, no significant biochemical changes were observed during muscle stimulation at 4 Hz. The results are discussed in terms of skeletal muscle "oxidative reserve", twitch tension maintenance and the relevance to the human diseased state of mitochondrial myopathy.
D000138:Acidosis / Q000139:chemically induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000473:pathology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone); D009861:Onium Compounds / Q000633:toxicity*; D010725:Phosphocreatine / Q000378:metabolism; D011808:Quinone Reductases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009861:Onium Compounds; D010725:Phosphocreatine; C007517:diphenyleneiodonium; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases