Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication

Golime, RamaRao; Bhattacharya, B. K.; Kumar, Subodh; Waghmare, Chandrakant

doi:10.1016/j.tox.2011.09.005

Cited by 19 publications

(10 citation statements)

References 37 publications

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“…Accumulated ACh resulting from OPinduced AChE inhibition has been linked to activation of a number of signal transduction mechanisms (Bodjarian et al, 1992;Savolainen and Hirvonen, 1992) that can contribute to time-dependent up-or downregulation of expression of genes that code for proteins involved in sustaining cell viability. In fact, toxicogenomic studies have reported that expression of genes linked to neuroprotective and neurodegenerative pathways is altered time dependently following an injection of rats with either a subconvulsive or a convulsive dose of sarin or soman (Damodaran et al, 2006;RamaRao et al, 2011;Spradling et al, 2011). In this respect, it is noteworthy that the frequency of sister chromatid exchanges was found to be significantly higher in human lymphocytes from victims of the 1995 sarin attack in Japan than in control subjects at two time points: 2-3 months and 3 years after the attack (Li et al, 2004).…”

Section: Molecular Mechanisms That Contribute To the Acute And Delayementioning

confidence: 99%

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Pereira

Aracava

DeTolla

et al. 2014

J Pharmacol Exp Ther

104

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The translational capacity of data generated in preclinical toxicological studies is contingent upon several factors, including the appropriateness of the animal model. The primary objectives of this article are: 1) to analyze the natural history of acute and delayed signs and symptoms that develop following an acute exposure of humans to organophosphorus (OP) compounds, with an emphasis on nerve agents; 2) to identify animal models of the clinical manifestations of human exposure to OPs; and 3) to review the mechanisms that contribute to the immediate and delayed OP neurotoxicity. As discussed in this study, clinical manifestations of an acute exposure of humans to OP compounds can be faithfully reproduced in rodents and nonhuman primates. These manifestations include an acute cholinergic crisis in addition to signs of neurotoxicity that develop long after the OP exposure, particularly chronic neurologic deficits consisting of anxiety-related behavior and cognitive deficits, structural brain damage, and increased slow electroencephalographic frequencies. Because guinea pigs and nonhuman primates, like humans, have low levels of circulating carboxylesterases-the enzymes that metabolize and inactivate OP compounds-they stand out as appropriate animal models for studies of OP intoxication. These are critical points for the development of safe and effective therapeutic interventions against OP poisoning because approval of such therapies by the Food and Drug Administration is likely to rely on the Animal Efficacy Rule, which allows exclusive use of animal data as evidence of the effectiveness of a drug against pathologic conditions that cannot be ethically or feasibly tested in humans.

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Section: Molecular Mechanisms That Contribute To the Acute And Delayementioning

confidence: 99%

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Pereira

Aracava

DeTolla

et al. 2014

J Pharmacol Exp Ther

104

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“… 2008 ; RamaRao et al. 2011 ). This implies that paraoxon does not sufficiently stimulate M 1 receptors in the hippocampus to induce ERK activation, and that paraoxon seizure-induced ERK activation is mediated by other receptors present in the hippocampus which are activated by the many neurotransmitters released during seizures.…”

Section: Discussionmentioning

confidence: 99%

Muscarinic M₁ receptor and cannabinoid CB₁ receptor do not modulate paraoxon‐induced seizures

Kow

Cheng

Jiang

et al. 2014

Pharmacology Res & Perspec

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One of the major signs of severe organophosphate poisoning is seizures. Previous studies have shown that both muscarinic agonist- and organophosphate-induced seizures require activation of muscarinic acetylcholine receptors in the central nervous system. Seizures induced by the muscarinic agonist pilocarpine require the M1 receptor and are modulated by cannabinoid CB1 receptors. In this study, we determined whether M1 and CB1 receptors also regulated seizures induced by the organophosphate paraoxon. We found no differences in seizures induced by paraoxon in wild-type (WT) and M1 knockout (KO) mice, indicating that in contrast to pilocarpine seizures, M1 receptors are not required for paraoxon seizures. Furthermore, we found that pilocarpine administration resulted in seizure-independent activation of ERK in the hippocampus in a M1 receptor-dependent manner, while paraoxon did not induce seizure-independent activation of ERK in the mouse hippocampus. This shows that pilocarpine and paraoxon activated M1 receptors in the hippocampus to different extents. There were no differences in seizures induced by paraoxon in WT and CB1 KO mice, and neither CB1 agonist nor antagonist administration had significant effects on paraoxon seizures, indicating that, in contrast to pilocarpine seizures, paraoxon seizures are not modulated by CB1 receptors. These results demonstrate that there are fundamental molecular differences in the regulation of seizures induced by pilocarpine and paraoxon.

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“…Although its exact prevalence is not known because it varies between populations, PACD was reported in only 2 to 10 percent of patients tested for photo allergy in North America and Europe, respectively. 199,200,201 A Chinese study by Gao and colleagues, however, found PABA-related PACD in 14.7% of 2,454 patients photo patch tested. 202 This variation could be related to PABA being used more frequently in Chinese cosmetics than in products marketed in North America and Europe.…”

Section: Pabamentioning

confidence: 99%

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

Johnson¹

2016

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Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication

Cited by 19 publications

References 37 publications

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Muscarinic M₁ receptor and cannabinoid CB₁ receptor do not modulate paraoxon‐induced seizures

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

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Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication

Cited by 19 publications

References 37 publications

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

Muscarinic M1 receptor and cannabinoid CB1 receptor do not modulate paraoxon‐induced seizures

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

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Muscarinic M₁ receptor and cannabinoid CB₁ receptor do not modulate paraoxon‐induced seizures