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Inhibition of heparin synthesis by methotrexate in rats in vivo

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Date
2002-07-15
Author
Marcondes, S.
Bau, E. C.
Antunes, E.
Dietrich, C. P.
Nader, H. B.
De Nucci, G.
Type
Artigo
ISSN
0006-2952
Is part of
Biochemical Pharmacology
DOI
10.1016/S0006-2952(02)01063-8
Metadata
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Abstract
The 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.
Citation
Biochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 64, n. 2, p. 169-175, 2002.
Keywords
mast cells
proteoglycans
heparin synthesis
compound 48/80
methotrexate
inflammation
URI
http://repositorio.unifesp.br/handle/11600/26930
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  • EPM - Artigos [17701]

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