Cooper J M, Petty R K, Hayes D J, Challiss R A, Brosnan M J, Shoubridge E A, Radda G K, Morgan-Hughes J A, Clark J B
Department of Biochemistry, Medical College of St. Bartholomew's Hospital, University of London, U.K.
J Neurol Sci. 1988 Feb;83(2-3):335-47. doi: 10.1016/0022-510x(88)90079-2.
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.
