ABSTRACT
Background: Methotrexate [MTX], as an anti-folate agent, is widely used in the treatment of rheumatic disorders and malignant tumors, however it damages reproductive sys- tem in mice. The aim of this research was to study the effects of ethyl pyruvate [EP] on embryo development and oxidative stress changes in the testis of mice treated with MTX
Materials and Methods: In this experimental study, thirty-two adult male Naval Medical Research Institute mice, with average weight of 26 +/- 2 g, were divided into four groups. The first group [control] received distilled water [0.1 ml/mice/day], while the second group was intraperitoneally [IP] treated with 20 mg/kg MTX once per week. The third group was IP treated with 40 mg/kg/day EP, and the fourth group was IP treated with both 20 mg/kg MTX and 40 mg/kg/day EP for 30 days. At the end of treatment fertilization rate and embryonic development were evaluated. Differences between these groups were assessed by ANOVA using the SPSS software package for Windows with a Tukey-Kramer multiple post-hoc comparison test
Results: MTX treatment caused significant [P<0.05] increase in malondialdehyde [MDA] and reduced catalase [CAT], as well as leading to in vitro fertilization [IVF] and embryonic development. The improved effects of EP on the IVF were determined by the reduced level of MDA [index of oxidative stress] and significant increased level of CAT [a key antioxidant]. We observed significant increase in fertilization rate and embryonic development in the treated group with both MTX and EP
Conclusion: It is suggested that EP can be useful in ameliorating testicular damages and embryotoxicity induced by MTX. These effects could be attributed to its antioxidant properties
ABSTRACT
Methotrexate [MTX] is an anti-metabolite drug widely used in treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The ester derivative, ethyl pyruvate [EP] is stable in solution and should function as an antioxidant and energy precursor. This study was conducted to evaluate the protective role of EP on sperm parameters, testosterone level and malondialdehyde [MDA] production in mice treated with MTX.32 adult male NMRI mice weighing 26 +/- 2 g were divided into 4 groups. Group 1 received 0.1 ml/mice/day of distilled water intraperitoneally for 30 days [ip]. Group 2 was treated with methotrexate at a dose of 20 mg/kg once a week [ip] for 30 days. Group 3 was treated with ethyl pyruvate at a dose of 40 mg/kg/daily [ip] for 30 days. Group 4 was treated with methotrexate [20 mg/kg] once a week simultaneously with ethyl pyruvate 40 mg/kg for 30 days. The results were analyzed by one-way ANOVA. A p<0.05 was considered to be significant. The results showed significant [p<0.05] decrease in sperm count and sperm motility as well as testosterone concentration while sperm with damaged DNA and MDA concentration in mice treated with MTX in comparison with control and MX+EP groups increased significantly [p<0.05]. Instead, MTX+EP group caused partial amelioration in all parameters mentioned above. Based on the present study, it can be concluded that MTX induced toxicity in sperm parameters and serum level of testosterone and increased MDA level. EP with its antioxidant properties could be administrated during treatment with MTX due to its protective effects on sperm parameters, plasma testosterone levels and lipid peroxidation