title: Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats.
abstract: OBJECTIVE
  To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction.
  
  
  METHODS
  In vivo study.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Adult male and female Sprague-Dawley rats.
  
  
  METHODS
  The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se).
  
  
  METHODS
  Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period.
  
  
  RESULTS
  At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels.
  
  
  CONCLUSIONS
  The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Kuwait University, Safat, Kuwait. Electronic address: knarayana@hsc.edu.kw.
authors.forename: Narayana
authors.initials: N
authors.lastname: Kilarkaje
authors.forename: Alyaa M
authors.initials: AM
authors.lastname: Mousa
authors.forename: Maie M
authors.initials: MM
authors.lastname: Al-Bader
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Khan
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001284:Atrophy; D001761:Bleomycin; D015153:Blotting, Western; D002945:Cisplatin; D019610:Cytoprotection; D004195:Disease Models, Animal; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005047:Etoposide; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012643:Selenium / Q000494:pharmacology; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013733:Testicular Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D006728:Hormones; D018809:Proliferating Cell Nuclear Antigen; D014168:Transferrin; D001761:Bleomycin; D005047:Etoposide; D024502:alpha-Tocopherol; D012643:Selenium; D015032:Zinc; D001205:Ascorbic Acid; D002945:Cisplatin
keywords: Anticancer drugs; male infertility; pituitary-testicular axis; sex hormones