Effects of dimethylformamide on in vivo fatigue and metabolism in rat skeletal muscle measured by 31P-NMR.
Dimethylformamide (DMF) is widely used as an industrial solvent in spite of well-established hepatotoxicity and adverse effects on in vitro muscle contractility. The doses used in the studies describing these effects were higher than the doses required to solubilize drugs to be injected at very low levels and the potential effects of DMF at very low levels has not yet been explored. The goal of this work was to study the effects of an acute, low dose of DMF (3 mu/100 g body weight, administered i.p.) on mechanical parameters and energy metabolism of contracting rat skeletal muscle. Metabolic changes were followed by 31P nuclear magnetic resonance spectroscopy. Tension was significantly lower during the fatigue test in DMF-treated rats than in controls. Phosphomonoesters and inorganic phosphorus level were lower, and intracellular pH was higher in DMF-treated rats than in controls, showing that energy metabolism was activated to a lesser degree, in relation with the lower mechanical performance, after DMF. Skeletal muscle is a target organ for dimethylformamide which has a major effect on muscle contractility by decreasing the tension developed. The effects of DMF suggest that it is unsuitable for use as a drug vehicle for in vivo injections, even at a very low nonhepatotoxic doses.
Le Tallec
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Laboratoire de RMN en Biologie et Médecine, LRMBM, Faculté de Médecine, Université Rennes I, France.
Lacroix
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de Certaines
J D
JD
Chagneau
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F
Levasseur
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R
Le Rumeur
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E
D000818:Animals; D004126:Dimethylformamide / Q000633:toxicity*; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D010755:Organophosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar
D010755:Organophosphates; D010725:Phosphocreatine; D010758:Phosphorus; D004126:Dimethylformamide