title: Radioprotective potential of melatonin against ⁶⁰Co γ-ray-induced testicular injury in male C57BL/6 mice.
abstract: BACKGROUND
  Melatonin, the chief secretary product of pineal gland, is a strong free radical scavenger and antioxidant molecule. The radioprotective efficacy and underlying mechanisms refer to its antioxidant role in somatic cells. The purpose of this study, therefore, was to investigate the prophylactic implications of melatonin against γ-ray-induced injury in germinal cells (testes). C57BL/6 male mice were administered melatonin (100 mg/kg) intra-peritoneally 30 min prior to a single dose of whole-body γ-irradiation (5 Gy, 1 Gy/minute) using (60)Co teletherapy unit. Animals were sacrificed at 2h, 4h and 8h post-irradiation and their testes along with its spermatozoa taken out and used for total antioxidant capacity (TAC), lipid peroxidation, comet assay, western blotting and sperm motility and viability. In another set of experiment, animals were similarly treated were sacrificed on 1(st), 3(rd), 7(th), 15(th) and 30(th) day post-irradiation and evaluated for sperm abnormalities and histopathological analysis.
  
  
  RESULTS
  Whole-body γ-radiation exposure (5 Gy) drastically depleted the populations of spermatogenic cells in seminiferous tubules on day three, which were significantly protected by melatonin. In addition, radiation-induced sperm abnormalities, motility and viability in cauda-epididymes were significantly reduced by melatonin. Melatonin pre-treatment significantly inhibited radiation-induced DNA strands breaks and lipid peroxidation. At this time, radiation-induces activation of ATM-dependent p53 apoptotic proteins-ATM, p53, p21, Bax, cytochrome C, active caspase-3 and caspases-9 expression, which were significantly reversed in melatonin pre-treated mice. This reduced apoptotic proteins by melatonin pre-treatment was associated with the increase of anti-apoptotic-Bcl-x and DNA repair-PCNA proteins in irradiated mice. Further, radiation-induced decline in the TAC was significantly reversed in melatonin pre-treated mice.
  
  
  CONCLUSIONS
  The present results indicated that melatonin as prophylactic agent protected male reproductive system against radiation-induced injury in mice. The detailed study will benefit in understanding the role of melatonin in modulation of radiation-induced ATM-dependent p53-mediated pro-vs.-anti apoptotic proteins in testicular injury. These results can be further exploited for use of melatonin for protection of male reproductive system in radiotherapy applications involving hemibody abdominal exposures.
authors.affiliation: Chemical Radioprotector and Radiation Dosimetry Research Group, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization, Brig. S. K. Mazumdar Road, New Delhi, Delhi, 110054, India. shahanshah88@hotmail.com.|Genome Biology Laboratory, Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India. shahanshah88@hotmail.com.
authors.forename: Shahanshah
authors.initials: S
authors.lastname: Khan
authors.affiliation: Chemical Radioprotector and Radiation Dosimetry Research Group, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization, Brig. S. K. Mazumdar Road, New Delhi, Delhi, 110054, India. adhikari_56@yahoo.co.in.
authors.forename: Jawahar Singh
authors.initials: JS
authors.lastname: Adhikari
authors.affiliation: Genome Biology Laboratory, Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India. Rizvi_ma@yahoo.com.
authors.forename: Moshahid Alam
authors.initials: MA
authors.lastname: Rizvi
authors.affiliation: Chemical Radioprotector and Radiation Dosimetry Research Group, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization, Brig. S. K. Mazumdar Road, New Delhi, Delhi, 110054, India. nkcinmas@rediffmail.com.
authors.forename: Nabo Kumar
authors.initials: NK
authors.lastname: Chaudhury
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D003037:Cobalt Radioisotopes; D016166:Free Radical Scavengers / Q000378:metabolism; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D013094:Spermatozoa / Q000187:drug effects / Q000528:radiation effects; D013737:Testis / Q000187:drug effects* / Q000293:injuries / Q000528:radiation effects; D014916:Whole-Body Irradiation
chemical_list: D051017:Apoptosis Regulatory Proteins; D003037:Cobalt Radioisotopes; D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D008550:Melatonin