Astaxanthin prevents the methotrexate-induced reproductive toxicity by targeting oxidative stress in male mice

Abstract

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. Biometric and semen parameters as well as, biochemical markers of oxidative stress were measured. 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. Thus, the current results suggest that 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.