Morphometric studies of specific brain regions of rats chronically intoxicated with the organophosphate methamidophos.

Subtle neurological disturbances have been described in organophosphorus intoxication. Experimental studies have reported neuronal necrosis, particularly in animals experiencing seizures. The objective of the present work was to investigate if in rats (without seizures) exposed to an organophosphate agent, morphological changes occur in specific regions of the brain. The animals received 2.5 or 5.0 mg/kg methamidophos once a week for 2 months and were decapitated after 2 months 7 days of drug administration. We observed atrophy of the molecular layer of the parietal cortex without neuronal loss in specific cerebral regions. This would be due to atrophy or loss of neuronal ramifications but without neuronal loss.

Protective effect of early and late administration of pralidoxime against organophosphate muscle necrosis.

The objective of the present investigation was to study the protection afforded by a single administration of pralidoxime against the muscle necrosis induced by the organophosphate compound metamidophos at different times after intoxication. The fiber necrosis of the diaphragm muscle was quantified by a morphometric technique, comparing the area fraction occupied by necrotic muscle fibers in animals that received pralidoxime at different times after intoxication, i.e., 0, 1, 3, 6, and 12 h. Pralidoxime administration protected metamidophos-induced muscle necrosis in all groups studied except for the 12-h group. The earlier the administration of pralidoxime the greater the protection against muscle necrosis. This protection was not accompanied by complete reactivation of plasma cholinesterase activity. Results support the current opinion that pralidoxime should be administered as soon as possible after organophosphate intoxication, because in addition to reversing the muscarinic effects, early administration of pralidoxime also prevents muscle necrosis--which could impair muscular function and respiratory condition. The time difference between recovery of plasma cholinesterase activity and muscle necrosis protection indicates that this method is not completely trustworthy for patient follow-up, since some improvement may occur in spite of the low plasma cholinesterase activity.

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. DESIGN: 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.