Impaired Mitochondrial Functions in Organophosphate Induced Delayed Neuropathy in Rats

Masoud, Anwar; Kiran, Ravi; Sandhir, Rajat

doi:10.1007/s10571-009-9420-4

Cited by 58 publications

(37 citation statements)

References 66 publications

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“…Typical signs and symptoms of OPIDN include tingling of the hands and feet, followed by sensory loss, progressive muscle weakness and flaccidity of the distal skeletal muscles of the lower and upper extremities and ataxia [3][4][5]. In pathology, OPIDN is classified as a centralperipheral sensorimotor axonopathy, which is characterized by distal axonal degeneration in spinal cord and peripheral nerves and swollen axons containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles [6,7]. At present, there is a lack of effective means to treat OPIDN, so it is very important to find new effective therapy means to treat OPIDN.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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“…The mechanism by which dichlorvos provokes myopathic and neurodegenerative effects has not been defined, but some work suggests that it is related to mitochondrial dysfunction [54]. The changes in metabolic processes and potential mitochondrial dysfunction (see below) observed in response to dichlorvos exposure make this a plausible mechanism for the damage induced in the worms.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of AChE is likely a key player as many of the perturbed processes involve neuronal signaling, and the observed behavior changes are consistent with increased accumulation of acetylcholine. The observed changes in the expression of genes involved in energy metabolism suggest that dichlorvos is disrupting mitochondrial function, which has been shown to be a mechanism for neuronal degeneration [54]. Calcium homeostasis is potentially another process perturbed by dichlorvos exposure, but it is unclear whether dichlorvos directly or indirectly perturbs calcium homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery

et al. 2013

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BackgroundThe principal toxicity of acute organophosphate (OP) pesticide poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethality—particularly through the inhibition of AChE—studies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.ResultsWe exposed cultures of worms in axenic, defined medium to dichlorvos under three exposure protocols. In the first, worms were exposed continuously throughout the experiment. In the second and third, the worms were exposed for either 2 or 8 h, the dichlorvos was washed out of the culture, and the worms were allowed to recover. We then analyzed gene expression using whole genome microarrays from RNA obtained from worms sampled at multiple time points throughout the exposure. The worms showed a time-dependent increase in the expression of genes involved in stress responses. Early in the exposure, the predominant effect was on metabolic processes, while at later times, an immune-like response and cellular repair mechanisms dominated the expression pattern. Following removal of dichlorvos, the gene expression in the worms appeared to relatively rapidly return to steady-state levels.ConclusionThe changes in gene expression observed in the worms following exposure to dichlorvos point towards two potential mechanisms of toxicity: inhibition of AChE and mitochondrial disruption.

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“…Study by Masoud et al also suggested that the activity of mitochondrial succinate dehydrogenase was obviously decreased in the brain of monocrotophos (MCP)-or dichlorvos (DDVP)-exposed rats and the activities of mitochondrial complex I (NADH dehydrogenase), II (succinate dehydrogenase), and IV (cytochrome oxidase) in isolated mitochondria from different brain regions were all significantly decreased. 21 As mentioned above, the oxidative stress of nervous system induced by TOCP might damage the mitochondrial Figure 6. The activity of mitochondrial succinate dehydrogenase by mitochondria from hens' nerve tissues following administration of tri-ortho-cresyl phosphate (TOCP).…”

Section: Atp Has Beenmentioning

confidence: 93%

Changes of mitochondrial ultrastructures and function in central nervous tissue of hens treated with tri-ortho-cresyl phosphate (TOCP)

et al. 2010

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Tri-ortho-cresyl phosphate (TOCP), an organophosphorus ester, is capable of producing organophosphorus ester-induced delayed neurotoxicity (OPIDN) in humans and sensitive animals. The mechanism of OPIDN has not been fully understood. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. Adult hens were treated with 750 mg/kg·bw TOCP by gavage and control hens were given an equivalent volume of corn oil. On day 1, 5, 15, 21 post-dosing, respectively, hens were anesthetized by intraperitoneal injection of sodium pentobarbital and perfused with 4% paraformaldehyde. The cerebral cortex cinerea and the ventral horn of lumbar spinal cord were dissected for electron microscopy. Another batch of hens were randomly divided into three experimental groups and control group. Hens in experimental groups were, respectively, given 185, 375, 750 mg/kg·bw TOCP orally and control group received solvent. After 1, 5, 15, 21 days of administration, they were sacrificed and the cerebrum and spinal cord dissected for the determination of the mitochondrial permeability transition (MPT), membrane potential (Δψ m) and the activity of succinate dehydrogenase. Structural changes of mitochondria were observed in hens’ nervous tissues, including vacuolation and fission, which increased with time post-dosing. MPT was increased in both the cerebrum and spinal cord, with the most noticeable increase in the spinal cord. Δψm was decreased in both the cerebrum and spinal cord, although there was no significant difference in the three treated groups and control group. The activity of mitochondrial succinate dehydrogenase assayed by methyl thiazolyl tetrazolium (MTT) reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The results suggested mitochondrial dysfunction might partly account for the development of OPIDN induced by TOCP.

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Impaired Mitochondrial Functions in Organophosphate Induced Delayed Neuropathy in Rats

Cited by 58 publications

References 66 publications

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery

Changes of mitochondrial ultrastructures and function in central nervous tissue of hens treated with tri-ortho-cresyl phosphate (TOCP)

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