Doxorubicin-induced testicular toxicity: possible underlying mechanisms and promising pharmacological treatments in experimental models.

Chemotherapy is considered to be the most effective intervention in cancer treatment. The first use of chemotherapy began in the 1940s, unfortunately, its use result in many serious and debilitating side effects which affect human daily activities. Doxorubicin is a powerful antineoplastic drug FDA-approved for the management of a variety of cancer types including leukemia and lymphoma. However, its clinical use is limited due to its toxic effect on different tissues including testicular toxicity which has a bad impact on the quality of life of cancer survivors. DOX-induced testicular toxicity is accompanied by defects in sperm analysis including low sperm count, low sperm motility, and high sperm abnormalities in addition to affecting steroidogenesis. This review is intended to discuss the pharmacodynamics and the pharmacokinetics of doxorubicin, besides the possible underlying mechanisms that may be contributed to the damage of testicles caused by DOX including oxidative stress, inflammation, apoptosis, and autophagy. Moreover, the assessment of post-chemotherapy testicular toxicity in animals and the promising pharmacological treatment that has been studied in animal models were discussed.