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Mitochondrial ATP synthase inhibition and nitric oxide are involved in muscle weakness that occurs in acute exposure of rats to monocrotophos
- Source :
- Toxicology Mechanisms and Methods
- Publication Year :
- 2009
-
Abstract
- Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD(50)) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-N(G) Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure.
- Subjects :
- medicine.medical_specialty
Insecticides
Health, Toxicology and Mutagenesis
Blotting, Western
chemistry.chemical_element
Skeletal muscle
Mitochondrion
Calcium
Toxicology
Nitric oxide
03 medical and health sciences
Nitroarginine
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Mitochondrial calcium uptake
Electrophoresis, Gel, Two-Dimensional
Rats, Wistar
Muscle, Skeletal
030304 developmental biology
Organophosphate poisoning
0303 health sciences
Muscle Weakness
biology
ATP synthase
Mitochondrial Proton-Translocating ATPases
3. Good health
Mitochondria, Muscle
Rats
Nitric oxide synthase
Endocrinology
medicine.anatomical_structure
chemistry
Biochemistry
Monocrotophos
Electron transport chain
biology.protein
Female
Cholinesterase Inhibitors
030217 neurology & neurosurgery
Research Article
Subjects
Details
- ISSN :
- 15376524
- Volume :
- 19
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Toxicology mechanisms and methods
- Accession number :
- edsair.doi.dedup.....738d4420ca31c87782fbb7a658cfa953