A Histochemical Study of Changes Observed in the Mouse Diaphragm after Organophosphate Poisoning

Abstract

<jats:p> A sublethal dose of sarin (GB, isopropyl methylphosphonofluoridate) was administered to mice. The animals were killed up to 28 d after dosing and frozen sections were made of the excised diaghragms which were stained using haematoxylin and eosin and a modified Gomori trichrome method. Muscle fibre degeneration and mononuclear infiltration were seen, notably at 24 h and 3 d. A number of histochemical procedures were carried out, including the GBHA procedure for ionized calcium. Calcium accumulation, seen at 4 h, was the earliest abnormality observed. All changes were rapidly regressing by 5 d and histological appearances were normal by 14 d. It was concluded that sarin produced myopathic changes preceded by calcium accumulation. </jats:p>

Sarin experiences in Japan: Acute toxicity and long-term effects

“…High CK level in severely affected subjects were secondary to a direct action with Sarin on skeletal muscles [1,6,8,15,25].…”

Protective Effect of Early and Late Administration of Pralidoxime against Organophosphate Muscle Necrosis

“…These authors suggested that hyperstimulation plays a role in myo"ber necrosis. Brigth et al (1991) observed calcium ions next to the neuromuscular junctions in muscle "bers of mice intoxicated with the organophosphate sarin and suggested that accumulation of this ion plays a role in muscle "ber necrosis. Calore et al (1999) reported inhibition of sarcoplasmic esterase and sarcoplamic lipase activity in animals intoxicated with the organophosphate isofenphos.…”

Miotoxicidade por organofosforados

“…Os vários autores citados na literatura, que estudaram experimentalmente a miopatia por organofosforados, utilizaram outras técnicas histológicas e histoquímicas, especialmente a coloração pelo tricrômico modificado de Gomori 4,13,14,15,17 . Brigth e col. 3 , 1991, estudaram a expressão da fosfatase ácida em músculos de animais intoxicados, porém sem finalidade de quantificar as lesões.…”

“…Alterações estruturais e funcionais observadas nos músculos esqueléticos estão relacionadas com as estruturas químicas dos produtos e com o tipo de músculo, sendo o diafragma o mais afetado em estudos experimentais 3,4,5,8,9,13,14,15 . Necrose muscular, semelhante à observada em animais de laboratório, foi encontrada em músculos diafragma e intercostais de indivíduos intoxicados pelo parathion 6 , diazinon 1 , triclornato 7 e combinação de malathion e diazinon 18 .…”