Paraoxon induced myopathy

Wecker, L., Dettham, W-D. (1976). Paraoxon-induced myopathy muscle specificity and acetylcholine involvement. Exp. Neurol. 51 281-91. 

De Bleecker, J. L., Van Den Abcele, K. G., and De Rcuck, J. L. (1992b). Variable involvement of rat. skeletal mu.sclc.s in paraoxon-induced necrotizing myopathy. Res. Commun. Paihol. Pharmacol. 75,309-322. 

Dc Bleecker, J. L., Metre, V. I., and Pappciis, S. (1998). Quinidinc prevents paraoxon-induced necrotizing myopathy in rats, NeuroTo.xicology 19, 833-838. 

The first direct evidence that NO was involved in OP-induced myopathy derived from experiments using inhibitors of NO synthase in combination with OP (Jcyarasasingam el ai, 2000). Rats injected with paraoxon showed a 90-foid increase in the number of dying muscle fibers when compared to controls. Coadministration of the nonspecific NOS inhibitor nitro-L-argininc tnethyl-c,ster (L-NAME) or with the specific neuronal NOS inhibitor 7-nitroindazolc (7-NI) dramatically reduced the number of myopathic fibers to 20% when compared to rats receiving paraoxon only. These data confirm that increased NO production is essentia in causing such a myopathy. 

Subsequent to the acute cholinergic manifestations of OP toxicity in humans, and approximately 24-96 hours after exposure, the onset of an "intermediate syndrome" which includes ocular effects has been recognised more recently for some OPs (Senanayake and Karalliedde, 1987 Karademir et aL, 1990). The associated clinical signs, which are characteristically different from those seen in OP-induced delayed pol)meuropathy, are paralysis and weakness of proximal limbs, respiratory, neck and cranial muscles, including those innervated by the oculomotor nerve. The occurrence of myopathy in rats exposed to diisopropylfluorophosphate, paraoxon or soman (Wecker et aL, 1978 Vanneste and Lison, 1993) resembled the features of the "intermediate syndrome". The severity and duration of the myopathy in rats appeared directly related to the degree of inhibition of AChE. 

A myopathy has been described post mortem in cases of human poisoning with organophosphates inter alia with parathion and also noted in experimental animals with soman, paraoxon and sarin " and it has been suggested that there might be a connection between this myopathy and IMS (see section 10.3.1.2). The myopathy appears to be initiated by calcium accumulation in the region of the motor endplate as a result of OP-induced acetylcholine accumulation. Karalliedde et al concluded that IMS was probably caused by down-regulation of cholinergic receptors and that there was no direct relationship of IMS and the myopathy. 

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