Protective effect of pralidoxime on muscle fiber necrosis induced by organophosphate compounds.
OBJECTIVE
To determine the protective effect of pralidoxime on muscle fiber necrosis induced by organophosphate acute intoxication in rats.


METHODS
Adult male Wistar rats were given oral organophosphate compounds dissolved in glycerol formal: dichlorvos, isofenphos, metamidophos, and diazinon. Half of the animals also received pralidoxime mesylate (20 mg/kg, intraperitoneal). Control animals received only the solvent. Twenty-four hours after treatment, the diaphragm muscle was collected for histological counts of necrotic muscle fibers in transverse sections.


RESULTS
Metamidophos- and isofenphos-treated animals showed the highest percentage of necrotic muscle fibers: 1.66 +/- 1.112 and 1.34 +/- 0.320, respectively. Diazinon-treated animals had a lower percentage of necrotic fibers: 0.40 +/- 0.032 (p < 0.05) compared to the first 2 products, and dichlorvos-treated animals showed the smallest: 0.05 +/- 0.021 (p < 0.05) when compared to the other 3 products. Pralidoxime reduced necrotic fibers about 20 times in metamidophos-treated animals, 10 times in isofenphos-treated animals and 6 times in diazinon-treated animals. Pralidoxime administration did not increase plasma cholinesterase activity in any group, although symptoms were reduced.


CONCLUSIONS
Oxime reduced diaphragmatic muscle necrosis in experimental organophosphate intoxication, despite little effect on plasma cholinesterase. Since respiratory insufficiency is an important cause of mortality and morbidity in organophosphate intoxications, early oxime administration may be particularly beneficial.
Instituto Adolfo Lutz, Divisão de Patologia, São Paulo, Brazil. calore@uol.com.br
M J
MJ
Cavaliere
F R
FR
Puga
E E
EE
Calore
N M
NM
Calore
J R
JR
Pelegrino
A R
AR
da Rosa
R
R
Weg
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology; D003976:Diazinon / Q000633:toxicity; D004006:Dichlorvos / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D009946:Organothiophosphorus Compounds / Q000633:toxicity; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000931:Antidotes; D007306:Insecticides; D009946:Organothiophosphorus Compounds; D011220:Pralidoxime Compounds; C035019:isofenphos; D004006:Dichlorvos; C014655:methamidophos; D000110:Acetylcholinesterase; C028797:pralidoxime; D003976:Diazinon