title: The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents.
abstract: 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.
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Emad
authors.initials: E
authors.lastname: Ghobadi
authors.affiliation: b Student Research Committee, Department of Immunology , School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Milad
authors.initials: M
authors.lastname: Moloudizargari
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|c Department of Pharmacology, Faculty of Medicine , Babol University of Medical Sciences , Babol , Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Asghari
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|d Toxicology and Diseases Group, Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D013090:Spermatocytes / Q000187:drug effects; D013733:Testicular Diseases / Q000139:chemically induced* / Q000517:prevention & control
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D020011:Protective Agents; D003520:Cyclophosphamide
keywords: Alkylating agent; DNA damage; cyclophosphamide; melatonin; oxidative stress; sperm toxicity