• Astaxanthin prevents the methotrexate-induced reproductive toxicity by targeting oxidative stress in male mice
  • Heidar Heidari Khoei,1 Sajad Fakhri,2 Siavash Parvardeh,3 Zahra Shams Mofarahe,4,* Mina Vardiani,5
    1. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
    3. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences,Tehran, Iran
    4. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    5. Infertility Center, Departmant of Obestetrics and Gynecology, Mazandaran University of Medical Sciences, Sari, Iran


  • Introduction: The future fertility of cancer patients after treatment is a serious concern amongst young cancer patients. Such chemotherapeutic agents as Methotrexate (MTX), a folic acid antagonist can cause long-term or permanent gonadal toxicity in male patients. Oxidative stress is a contributing mechanism to MTX-induced testicular damage. In the past decade, several studies have investigated the use of natural antioxidant agents to prevent the side effects of MTX. Astaxanthin (AST), a red-orange xanthophyll carotenoid, owns various clinical benefits and pharmacological effects including antioxidant, anti-tumor, anti-cancer, anti-diabetic, and anti-inflammatory properties. Since there has been no study so far in the literature on the effects of AST on MTX-induced testicular dysfunction, the present study evaluated the ameliorating effect of AST against MTX induced testicular dysfunction.
  • Methods: Thirty male mice were randomly divided into 5 groups including: control (received olive oil via oral gavage for 6 consecutive days), MTX (30 mg/kg MTX on the 7th day of the experiment), MTX+AST25 (received 25 mg/kg/day AST dissolved in olive oil for 6 consecutive days as well as, 30 mg/kg MTX on the 7th day of the experiment), MTX+AST 50 (received 50mg/kg/day AST dissolved in olive oil for 6 consecutive days as wellas, 30 mg/kg MTX on the 7th day of the experiment), MTXþ+ST 100 (received 100mg/kg/day AST dissolved in olive oil for 6 consecutive days as well as, 30 mg/kg MTX on the 7th day of the experiment). The animals were weighed before and after the experiment. At the end of the experiment (6 weeks after the last day of treatment), the animals were euthanized using CO2 gas and their testis and epididymis were dissected out. The cauda of epididymis was used for the evaluation of sperm parameters. The testis tissues were weighed and kept at -70˚C for biochemical analyses.
  • Results: Compared to the control group, MTX-treated group showed a significant decrease in sperm count, motility, viability, morphology, superoxide dismutase (SOD) and catalase (CAT) activities, and a significant increase in MDA levels. Pretreatment with AST for six consecutive days before MTX administration prevented these oxidative parameters.
  • Conclusion: MTX seems to impair the male fertility through oxidative damage in one hand, and AST pretreatment might improve the male fertility by preventing oxidative stress-induced fertility disorders, on the other hand. However, AST pretreatment might also protect germ cells against MTX-induced oxidative stress.
  • Keywords: Testicular toxicity, male infertility, Methotrexate, Asthaxantin