Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyrimethamine's antifertility effects in the male mouse suggest that this agent has potential as a male contraceptive. This dihydrofolate reductase inhibitor was administered to 72 adult male Swiss-Webster mice over a 50-day period at dosages ranging from 10-200 mg/kg/day. During the last 10 days of drug administration, the study mice were exposed to 3 female mice who underwent 2 reproductive cycles. The female mice were examined for gravidity 19 days after the onset of the breeding cycle. Male infertility was dose-dependent, with no pregnancies occurring among the partners of mice who received the maximum dosage of pyrimethamine. Also inversely proportional to dosage were the number and motility of epididymal sperm in the treated mice and mean seminiferous tubule diameter and testicular and epididymal weights. Time course analysis revealed that the drug begins to exert its antifertility effect 33 days after administration and nearly complete infertility is achieved with 50 days, suggesting that pyrimethamine acts on early-midspermatogenesis. All mice returned to normal fertility status 44 days after treatment ended, and epididymal sperm reserves, sperm motility, and testicular and epididymal weights also returned to baseline values within this time period. Of particular interest was the finding that when pyrimethamine was administered to another group of mice for 80 days, infertility was significantly reduced beyond that achieved in 50 days, yet there were no further effects on testicular epididymal function. It would appear that pyrimethamine's mechanism of action is its antifolate action, with the main effect occurring on the testes rather than the epididymis.
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PMID:Pyrimethamine: an approach to the development of a male contraceptive. 230 8

We had previously found that 2,4-diaminopyrimidines affected spermatogenesis, possibly through the inhibition of testicular dihydrofolate reductase (DHFR). The current study examined the effects of etoprine, a highly lipophilic 2,4-diaminopyrimidine that is also a potent DHFR inhibitor, on the fertility of male mice at various dosages (0.1-50 mg/kg/day) for 55 days and male rats at 5 mg/kg/day for 65 days. Two other substituted diaminopyrimidines were tested at dosages of 50 mg/kg/day for 55 days. Results of breeding trials along with assessment of various parameters indicative of male fertility were noted. We found that of the compounds tested, etoprine is a potent antifertility agent that causes complete infertility at doses of > or = 5 mg/kg/day in mice with a threshold of effectiveness occurring between 1 and 5 mg/kg/day. The antifertility action of etoprine may be related to its capacity to inhibit testicular DHFR and its high degree of lipophilicity.
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PMID:The contraceptive effects of etoprine on male mice and rats. 755 48

Methotrexate (MTX; 4-amino-10-methylfolic acid) is a folic acid reductase inhibitor used to treat autoimmune diseases and certain types of cancer. Testicular toxicity resulting from MTX is a significant side effect that may cause subsequent infertility. The present study was conducted to examine the ameliorating effects of vitamin B17 (VitB17) against testicular toxicity induced by MTX in male rats. A total of 50 male albino rats were equally divided into five groups [control group; vitamin B17 group (VitB17) administered VitB17 only; methotrexate group administered MTX only; cotreated group, (VitB17+MTX) and posttreated group (MTX+VitB17)]. In methotrexate group (MTX), a significant decrease was observed in body weight and the testicular weight, as well as the levels of plasma testosterone, luteinizing hormone and follicle-stimulating hormone compared with control. The sperm count, viability, morphology index, total motility, and progressive motility also decreased in MTX rats compared with control. Furthermore, the levels of reduced glutathione, catalase, and superoxide dismutase, as well as proliferating cell nuclear antigen protein expression, in the testicular tissue decreased in MTX compared with control. In addition, MTX caused a significant increase in DNA and tissue damage compared with control. However, VitB17 ameliorated these effects, indicating that it has a preventative and curative effect against MTX-induced reproductive toxicity in male rats. The protective effect of VitB17 may be associated to its antioxidant properties as it possibly acts as a free-radical scavenger and lipid peroxidation inhibitor, as well as its protective effect on the levels of GSH, SOD, and CAT.
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PMID:Vitamin B17 Ameliorates Methotrexate-Induced Reproductive Toxicity, Oxidative Stress, and Testicular Injury in Male Rats. 3319 2