The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents

ABSTRACT

Introduction: Cyclophosphamide (CP) is an alkylating antineoplastic agent with known toxicity to the male reproductive system.

Areas covered: This review summarizes the known mechanisms by which CP exerts its toxic effects on the male reproductive system and the methods utilized to prevent such effects so that it could be further investigated and applied in clinical use. Keywords including [‘Cyclophosphamide’ AND ’male reproductive’ OR’ sperm toxicity’ OR ’spermatotoxicity’ OR ’infertility] were searched through Google Scholar, PubMed and Scopus databases based on PRISMA guidelines. After removing duplicates and irrelevant data, 76 papers were reviewed concerning the outcomes of treatment of male mice, rats, and humans with CP and the effects of co-administration of various natural and synthetic compounds on male reproductive system.

Expert opinion: CP exerts its effect mainly by inducing oxidative stress and changing gene expression in spermatocytes variably during different stages of development. These effects could be either restored or prevented by the administration of compounds with antioxidant properties and those which target the biochemical alterations induced by CP.

KEYWORDS:

• Alkylating agent
• cyclophosphamide
• sperm toxicity
• oxidative stress
• DNA damage
• melatonin

Article highlights

• The review delineates the mechanisms of cyclophosphamide gonadal toxicities under several categories and displays the interplay between these pathways.

• Various substances which have proven to be useful in preventing the toxic effects are investigated and the possible mechanisms involved in such effects are discussed.

• The pathways discussed in this paper could be used for a rational approach to the matter of protecting the male reproductive system from the toxic effects of cyclophosphamide.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.

Notes on contributors

Emad Ghobadi

EGH and MHA participated in the literature search and drafted the article; MM participated in drafting and editing the article. All authors were involved in data analysis and interpretation. MA conceived and supervised the whole study. All authors have read and approved the final version.

Milad Moloudizargari

EGH and MHA participated in the literature search and drafted the article; MM participated in drafting and editing the article. All authors were involved in data analysis and interpretation. MA conceived and supervised the whole study. All authors have read and approved the final version.

Mohammad Hossein Asghari

EGH and MHA participated in the literature search and drafted the article; MM participated in drafting and editing the article. All authors were involved in data analysis and interpretation. MA conceived and supervised the whole study. All authors have read and approved the final version.

Mohammad Abdollahi

EGH and MHA participated in the literature search and drafted the article; MM participated in drafting and editing the article. All authors were involved in data analysis and interpretation. MA conceived and supervised the whole study. All authors have read and approved the final version.