Biochemical, histopathological and clinical evaluation of delayed effects caused by methamidophos isoforms and TOCP in hens: Ameliorative effects using control of calcium homeostasis

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dc.contributor.authorEmerick, Guilherme Luz [UNESP]
dc.contributor.authorEhrich, Marion
dc.contributor.authorJortner, Bernard S.
dc.contributor.authorOliveira, Regina V.
dc.contributor.authorDeOliveira, Georgino H. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionVirginia Polytech Inst & State Univ
dc.date.accessioned2014-05-20T13:25:33Z
dc.date.available2014-05-20T13:25:33Z
dc.date.issued2012-12-08
dc.description.abstractThis work evaluated the potential of the isoforms of methamidophos to cause organophosphorus-induced delayed neuropathy (OPIDN) in hens. In addition to inhibition of neuropathy target esterase (NTE) and acetylcholinesterase (AChE), calpain activation, spinal cord lesions and clinical signs were assessed. The isoforms (+)-, (+/-)- and (-)-methamidophos were administered at 50 mg/kg orally; tri-ortho-cresyl phosphate (TOCP) was administered (500 mg/kg, po) as positive control for delayed neuropathy. The TOCP hens showed greater than 80% and approximately 20% inhibition of NTE and AChE in hen brain, respectively. Among the isoforms of methamidophos, only the (+)-methamidophos was capable of inhibiting NTE activity (approximately 60%) with statistically significant difference compared to the control group. Calpain activity in brain increased by 40% in TOCP hens compared to the control group when measured 24h after dosing and remained high (18% over control) 21 days after dosing. Hens that received (+)-methamidophos had calpain activity 12% greater than controls. The histopathological findings and clinical signs corroborated the biochemical results that indicated the potential of the (+)-methamidophos to be the isoform responsible for OPIDN induction. Protection against OPIDN was examined using a treatment of 2 doses of nimodipine (1 mg/kg, i.m.) and one dose of calcium gluconate (5 mg/kg, iv.). The treatment decreased the effect of OPIDN-inducing TOCP and (+)-methamidophos on calpain activity, spinal cord lesions and clinical signs. (C) 2012 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, Araraquara, SP, Brazil
dc.description.affiliationUniversidade Federal de São Carlos (UFSCar), Dept Chem, São Carlos, SP, Brazil
dc.description.affiliationVirginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA
dc.description.affiliationUnespUniv Estadual Paulista UNESP, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, Araraquara, SP, Brazil
dc.format.extent88-95
dc.identifierhttp://dx.doi.org/10.1016/j.tox.2012.08.002
dc.identifier.citationToxicology. Clare: Elsevier B.V., v. 302, n. 1, p. 88-95, 2012.
dc.identifier.doi10.1016/j.tox.2012.08.002
dc.identifier.issn0300-483X
dc.identifier.urihttp://hdl.handle.net/11449/8103
dc.identifier.wosWOS:000309642600012
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofToxicology
dc.relation.ispartofjcr3.265
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectChiral organophosphate pesticidesen
dc.subjectMethamidophosen
dc.subjectAcetylcholinesteraseen
dc.subjectNeuropathy target esteraseen
dc.subjectCalpainen
dc.subjectTreatment of OPIDNen
dc.titleBiochemical, histopathological and clinical evaluation of delayed effects caused by methamidophos isoforms and TOCP in hens: Ameliorative effects using control of calcium homeostasisen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.orcid0000-0002-5061-5957[4]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt
unesp.departmentPrincípios Ativos Naturais e Toxicologia - FCFpt

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Araraquara - FCF - Faculdade de Ciências Farmacêuticas