Journal article
Cytotoxic and genotoxic effects of methotrexate in germ cells of male Swiss mice
Mutation research. Genetic toxicology and environmental mutagenesis, Vol.655(1-2), pp.59-67
2008
DOI: 10.1016/j.mrgentox.2008.07.003
PMID: 18678279
Abstract
Methotrexate (MTX) is an anti-metabolite drug widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. Developed as an analogue of folic acid, it inhibits purine and pyrimidine synthesis that accounts for its therapeutic efficacy as well as for its toxicities. MTX has narrow therapeutic index and its toxicity has been reported in various organ systems including gastrointestinal, haematologic and central nervous system. The objective of the present study is to investigate the germ cell toxicity induced by MTX in male Swiss mice. MTX was administered intraperitoneally (ip) at the doses of 5, 10, 20 and 40 mg/kg to mice (20–25 g) weekly once (wk) for 5 and 10 weeks. The animals were sacrificed 1 week after receiving the last treatment of MTX. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. MTX treatment significantly reduced the sperm count and increased the occurrence of sperm head abnormalities in a dose dependent manner. It induced the testicular toxicity as evident from the histology of testis. Sperm comet, TUNEL and halo assay in testis also revealed significant DNA damage after MTX treatment. On the basis of the present study, it can be concluded that MTX induced germ cell toxicity in mice.
Details
- Title: Subtitle
- Cytotoxic and genotoxic effects of methotrexate in germ cells of male Swiss mice
- Creators
- S Padmanabhan - National Institute of Pharmaceutical Education and ResearchD. N Tripathi - National Institute of Pharmaceutical Education and ResearchA Vikram - National Institute of Pharmaceutical Education and ResearchP Ramarao - National Institute of Pharmaceutical Education and ResearchG. B Jena - National Institute of Pharmaceutical Education and Research
- Resource Type
- Journal article
- Publication Details
- Mutation research. Genetic toxicology and environmental mutagenesis, Vol.655(1-2), pp.59-67
- Publisher
- Elsevier
- DOI
- 10.1016/j.mrgentox.2008.07.003
- PMID
- 18678279
- ISSN
- 1383-5718
- eISSN
- 1879-3592
- Language
- English
- Date published
- 2008
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359697802771
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