Inhibition of heparin synthesis by methotrexate in rats in vivo

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dc.contributor.authorMarcondes, S.
dc.contributor.authorBau, E. C.
dc.contributor.authorAntunes, E.
dc.contributor.authorDietrich, C. P.
dc.contributor.authorNader, H. B.
dc.contributor.authorDe Nucci, G.
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:33:27Z
dc.date.available2016-01-24T12:33:27Z
dc.date.issued2002-07-15
dc.description.abstractThe content and synthesis of heparin and mast cell-dependent skin oedema (as an indirect evaluation of histamine and serotonin content) were investigated in the rat skin after chronic treatment with compound 48/80, a mast cell degranulating substance. the effect of methotrexate, a folic acid analogue that interrupts the synthesis of DNA and RNA, on heparin synthesis and amine storage also was evaluated in rat skin. the heparin content at 6 and 240 hr after treatment with compound 48/80 was reduced markedly (86 and 64%, respectively). At 6 hr, heparin synthesis increased 3.1-fold compared with control animals; maximal synthesis occurred at 24 hr post-treatment (12.8-fold increase), decaying at 240 hr (2.4-fold increase). the dermatan sulfate content and synthesis were not affected by treatment with compound 48/80. Autoradiographic analysis revealed that methotrexate (2.5 mg/kg for 3 consecutive days) abolished heparin synthesis at 6, 24, and 72 hr after compound 48/80 treatment, without affecting dermatan sulfate synthesis. the oedema induced by intradermal injection of compound 48/80 (1 mug/site) into the rat skin was decreased significantly at 6 hr after chronic treatment with this compound, but was restored completely 72 hr post-treatment. This pattern of oedematogenic response was also observed in the methotrexate-treated rats. in conclusion, our results show that methotrexate suppresses heparin synthesis without affecting the synthesis of either dermatan sulfate or the co-stored amines histamine/serotonin (as evaluated by measuring the mast cell-dependent oedema), suggesting that the enzyme system involved in heparin synthesis is inducible. (C) 2002 Elsevier Science Inc. All rights reserved.en
dc.description.affiliationUniv Estadual Campinas, Fac Med Sci, Dept Pharmacol, BR-13081970 Campinas, SP, Brazil
dc.description.affiliationUNIFESP, Dept Bioquim, Escola Paulista Med, BR-04044020 São Paulo, SP, Brazil
dc.description.affiliationUnifespUNIFESP, Dept Bioquim, Escola Paulista Med, BR-04044020 São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent169-175
dc.identifierhttp://dx.doi.org/10.1016/S0006-2952(02)01063-8
dc.identifier.citationBiochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 64, n. 2, p. 169-175, 2002.
dc.identifier.doi10.1016/S0006-2952(02)01063-8
dc.identifier.issn0006-2952
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/26930
dc.identifier.wosWOS:000177233400002
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiochemical Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectmast cellsen
dc.subjectproteoglycansen
dc.subjectheparin synthesisen
dc.subjectcompound 48/80en
dc.subjectmethotrexateen
dc.subjectinflammationen
dc.titleInhibition of heparin synthesis by methotrexate in rats in vivoen
dc.typeinfo:eu-repo/semantics/article
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