Cavaliere MJ

References (3)

Title : Protective effect of early and late administration of pralidoxime against organophosphate muscle necrosis - Santos_2002_Ecotoxicol.Environ.Saf_53_48
Author(s) : Santos RP , Cavaliere MJ , Puga FR , Narciso ES , Pelegrino JR , Calore EE
Ref : Ecotoxicology & Environmental Safety , 53 :48 , 2002
Abstract : 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.
ESTHER : Santos_2002_Ecotoxicol.Environ.Saf_53_48
PubMedSearch : Santos_2002_Ecotoxicol.Environ.Saf_53_48
PubMedID: 12481856

Title : Early expression of ubiquitin in myofibers of rats in organophosphate intoxication - Calore_1999_Ecotoxicol.Environ.Saf_43_187
Author(s) : Calore EE , Sesso A , Puga FR , Cavaliere MJ , Calore NM , Weg R
Ref : Ecotoxicology & Environmental Safety , 43 :187 , 1999
Abstract : The degenerative process of the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos, a compound that inhibits esterases, was studied at different intervals of intoxication. Early disorganization of the intermyofibrillar network and of the myofilaments, as well as dilatation of organelles, were observed by use of transmission electron microscopy. These changes precede macrophage invasion of the muscle fibers. Early expression of ubiquitin was observed in segments of muscle fibers by immunohistochemistry. Bands of polyubiquitin complexes in muscle homogenates were observed by immunoblotting. These bands disappeared in later stages of intoxication. A 42.5-kDa band corresponds to actin, as observed by immunoblotting using antisarcometric actin. This indicates relatively large amounts of polyubiquitin complex associated with sarcomeric actin in muscle fibers in early stages of intoxication. Based on these results it seems that actin is an important target in organophosphate-induced myofiber degradation and that the degradation of this protein-by the polyubiquitin pathway-may play an important role in the early disorganization of the sarcomere, as observed by electron microscopy. A possible role of the ubiquitin proteolytic pathway is that of trying to eliminate proteins modified in the early phases of muscle fiber degeneration, which is a necessary step for regeneration of the posterior segmental muscle.
ESTHER : Calore_1999_Ecotoxicol.Environ.Saf_43_187
PubMedSearch : Calore_1999_Ecotoxicol.Environ.Saf_43_187
PubMedID: 10375421

Title : Protective effect of pralidoxime on muscle fiber necrosis induced by organophosphate compounds - Cavaliere_1998_J.Toxicol.Clin.Toxicol_36_295
Author(s) : Cavaliere MJ , Puga FR , Calore EE , Calore NM , Pelegrino JR , da Rosa AR , Weg R
Ref : Journal of Toxicology Clinical Toxicology , 36 :295 , 1998
Abstract : 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.
ESTHER : Cavaliere_1998_J.Toxicol.Clin.Toxicol_36_295
PubMedSearch : Cavaliere_1998_J.Toxicol.Clin.Toxicol_36_295
PubMedID: 9711194