Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid.

作者: S. Padmanabhan , D.N. Tripathi , A. Vikram , P. Ramarao , G.B. Jena

DOI: 10.1016/J.MRGENTOX.2008.11.011

关键词:

摘要: Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy inhibition dihydrofolate reductase (DHFR), a key enzyme folic acid (FA) metabolism. FA water-soluble vitamin which involved synthesis purines pyrimidines, essential precursors DNA. Folinic (FNA) reduced form that circumvents DHFR. Folate supplementation during MTX therapy psoriasis inflammatory reduces both toxicity side effects without compromising efficacy. Further, FNA common juvenile idiopathic arthritis. are reported to have protective on MTX-induced genotoxicity somatic cells; however their germ cells not been much explored. Previously, we evaluated cytotoxic genotoxic mice. In present study, intervened protection cell induced by male swiss animals were pre-treated with at doses 50, 100 200 microg/kg 4 consecutive days per week day five; was administered dose 20mg/kg once. 2.5, 5 10 mg/kg, 6 h (h) after single administration 20 mg/kg. dosing regimen continued up weeks. using testes weight (wt), sperm count, head morphology, comet assay, histology, TUNEL halo assay testis. results clearly demonstrate prior post-treatment as evident from decreased abnormalities, seminiferous tubule damage, DNA positive increased counts. report ameliorate

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