Sarcoplasmic lipase and non-specific esterase inhibition in myofibers of rats intoxicated with the organophosphate isofenphos.
The expression of sarcoplasmic esterases, lipases as well as the lipid content in the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos was studied. Lipid accumulation was documented at light, electron microsopic and by morphometric studies. The distribution of these lipid droplets was irregular and abundant in myofibers with numerous mitochondria (predominantly oxidative fibers). Histochemical inhibition of sarcoplasmic esterases and lipases was observed in the intoxicated animals. This sarcoplasmic inhibition of esterases occurs roughly in parallel to the inhibition of plasma cholinesterase activity. The inhibition of sarcoplasmic lipases may explain, at least partially, the accumulation of lipids. This inhibition probably makes difficult the use of lipids as fuel, especially in the oxidative fibers. In contrast to the small amount of muscle necrosis, (1.30+/-0.745), metabolic muscle impairment was intense and extensive, i.e., decreased activities of esterases and lipases in the sarcoplasm, that should contribute to muscle weakness. Therefore, because segmental necrosis was most prominent in oxidative fibers (and these fibers use lipids as the principal fuel and contain the greater amount of lipases in the sarcoplasm), it is possible that inhibition of activity of lipases is responsible for the segmental necrosis. Although the exact role of these metabolic changes is not known, it is possible that they contribute not only to the induction and evolution of muscle cell necrosis but also to the muscle weakness and clinical impairment of animals and humans in the acute intoxication by these compounds.
Laboratory of Molecular Pathology, Faculty of Medicine, University of São Paulo, SP, Brazil.
E E
EE
Calore
A
A
Sesso
F R
FR
Puga
M J
MJ
Cavaliere
N M
NM
Calore
R
R
Weg
D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002802:Cholinesterases / Q000097:blood; D003964:Diaphragm; D006651:Histocytochemistry; D007306:Insecticides / Q000633:toxicity*; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D009336:Necrosis; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000201:enzymology* / Q000648:ultrastructure
D007306:Insecticides; D009946:Organothiophosphorus Compounds; C035019:isofenphos; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D008049:Lipase; D002802:Cholinesterases