Attenuation of Methotrexate-Induced Embryotoxicity and Oxidative Stress by Ethyl Pyruvate

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.