Treatment of experimental NADH ubiquinone reductase deficiency with menadione.
Chronic administration of diphenylene iodonium (DPI) to rats has been shown to model the characteristics of mitochondrial myopathy. Using this model the efficacy of menadione therapy has been assessed. Menadione treatment of rats injected with DPI was associated with improved weight gain and increased survival rate. This was accompanied by an improvement in muscle function as judged by analysis of isometric twitch tension of the gastrocnemius muscle (1 Hz for 20 min). The decline in phosphocreatine (PCr) levels in the gastrocnemius muscle during stimulation and delayed recovery in PCr after stimulation were similar in the menadione treated and untreated models. Menadione treatment of the DPI model resulted in a resting intramuscular pH significantly lower than control or untreated DPI rats, but a similar decline in intramuscular pH to the DPI rats during stimulation. The changes in metabolite levels were broadly similar in both the menadione treated and untreated DPI models following stimulation, although the changes, except for increased lactate concentration, were generally less marked in the menadione-treated DPI model.
Cooper
J M
JM
Department of Neuroscience, Royal Free Hospital School of Medicine, London, UK.
Hayes
D J
DJ
Challiss
R A
RA
Morgan-Hughes
J A
JA
Clark
J B
JB
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004579:Electron Transport; D042967:Electron Transport Complex I; D006614:Hindlimb; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017240:Mitochondrial Myopathies / Q000188:drug therapy* / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency*; D009861:Onium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014812:Vitamin K / Q000008:administration & dosage / Q000627:therapeutic use*
D001713:Biphenyl Compounds; D009861:Onium Compounds; D010710:Phosphates; D010725:Phosphocreatine; C031291:diphenyliodonium; D014812:Vitamin K; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I