title: Protective role of taurine against genotoxic damage in mice treated with methotrexate and tamoxfine.
abstract: The genotoxic actions of anti-neoplastic drugs can lead to the development of secondary cancers in patients in extended remission. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine, on the genotoxicity of two well known anti-neoplastic drugs methotrexate (MTX) and tamoxifen (TAM) in Swiss albino mice. The animals were randomly divided into six groups consisting of ten mice each. Two groups were received single intraperitoneal injection of MTX (10 mg/kgb.wt.) and TAM (50 mg/kgb.wt.) to induce genotoxicity. Two other groups were treated orally with taurine (100 mg/kgb.wt.) for nine days prior to MTX and TAM administration. A vehicle treated control group and taurine control groups were also included. The protective effects of taurine were monitored by apoptosis assays and level of reduced glutathione (GSH), a key antioxidant, in liver, chromosomal aberrations in somatic and germ cells as well as sperm count, motility and morphology. The results indicated that taurine pre-treatment showed significant increment in the levels of GSH content, reduction in DNA fragmentation and ladder formation in hepatic tissue, suggesting the antioxidant activity of taurine may reduce the toxic effects of MTX and TAM. Treatment with taurine showed also significant reduction in the frequency of chromosomal aberrations in both somatic and germ cells. Moreover, it increases sperm count and motility, and decreases the incidence of sperm abnormalities. In conclusion, it appears that taurine protects against anti-neoplastic drugs-induced genotoxicity in somatic and germ tissues and may be of therapeutic potential in alleviating the risk of secondary tumors in chemotherapy.
authors.affiliation: Cell Biology Department, National Research Center, El Tahrir Street, 12622 Dokki, Giza, Egypt. dr sallyalam@yahoo.com
authors.forename: Sally S
authors.initials: SS
authors.lastname: Alam
authors.forename: Nagla A
authors.initials: NA
authors.lastname: Hafiz
authors.forename: Abeer H
authors.initials: AH
authors.lastname: Abd El-Rahim
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D016587:Antimutagenic Agents; D018931:Antineoplastic Agents, Hormonal / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D002869:Chromosome Aberrations / Q000187:drug effects; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D005854:Germ Cells / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051379:Mice; D013081:Sperm Motility / Q000187:drug effects; D013090:Spermatocytes / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013629:Tamoxifen / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D013654:Taurine / Q000494:pharmacology*
chemical_list: D000728:Androgens; D000964:Antimetabolites, Antineoplastic; D016587:Antimutagenic Agents; D018931:Antineoplastic Agents, Hormonal; D013438:Sulfhydryl Compounds; D013629:Tamoxifen; D013654:Taurine; D005978:Glutathione; D008727:Methotrexate