title: Zinc protects cyclophosphamide-induced testicular damage in rat: involvement of metallothionein, tesmin and Nrf2.
abstract: The role of zinc (Zn) in the protection of germ cells against testicular toxicants has long been elucidated, but the exact molecular mechanisms have not yet been explored. Cyclophosphamide (CP), one of the most commonly used anticancer drugs survived ages of treatment, but the unwanted toxicity limits its clinical usage. The present investigation was aimed to explore the role of Zn and its associated pathways in CP-induced testicular toxicity in S.D. rat. CP was administered in saline 30 mg/kg 5× weekly for 3 weeks (total dose of 450 mg/kg) by i.p. route, while Zn was supplemented by oral route at the doses of 1, 3, 10mg/kg/day for 3 weeks. CP significantly reduced Zn levels in serum and testes, body and testicular weight, sperm count and motility, spermiogenic cells, plasma testosterone and significantly increased the oxidative stress, sperm head abnormalities, sperm DNA damage with decreased chromatin and acrosome integrity; while Zn supplementation ameliorated the same. The present results demonstrated that Zn supplementation protected against CP-induced testicular damages by modulating metallothionein (MT), tesmin and Nrf2 associated pathways. Thus Zn supplementation during anticancer therapy might be potentially beneficial in reducing the off target effects associated with oxidative stress.
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India. Electronic address: mkrishnaprahlad@gmail.com.
authors.forename: Krishna Prahlad
authors.initials: KP
authors.lastname: Maremanda
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India. Electronic address: ksabbir25@gmail.com.
authors.forename: Sabbir
authors.initials: S
authors.lastname: Khan
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India. Electronic address: gbjena@gmail.com.
authors.forename: Gopabandhu
authors.initials: G
authors.lastname: Jena
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects*; D004249:DNA Damage / Q000187:drug effects; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013739:Testosterone / Q000097:blood; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D051265:NF-E2-Related Factor 1; D020011:Protective Agents; C119112:tesmin; D013739:Testosterone; D003520:Cyclophosphamide; D008668:Metallothionein; D015032:Zinc
keywords: Cyclophosphamide; Metallothionein; Nrf2; Rat testes; Tesmin; Zinc