title: Melatonin attenuates60Co γ-ray-induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice.
abstract: Protection of hematopoietic, immunological, and gastrointestinal injuries from deleterious effects of ionizing radiation is prime rational for developing radioprotector. The objective of this study, therefore, was to evaluate the radioprotective potential of melatonin against damaging effects of radiation-induced hematopoietic, immunological, and gastrointestinal injuries in mice. C57BL/6 male mice were intraperitoneally administered with melatonin (50-150 mg/kg) 30 min prior to whole-body radiation exposure of 5 and 7.5 Gy using60Co-teletherapy unit. Thirty-day survival against 7.5 Gy was monitored. Melatonin (100 mg/kg) pretreatment showed 100% survival against 7.5 Gy radiation dose. Melatonin pretreatment expanded femoral HPSCs, and inhibited spleenocyte DNA strands breaks and apoptosis in irradiated mice. At this time, it also protected radiation-induced loss of T cell sub-populations in spleen. In addition, melatonin pretreatment enhanced crypts regeneration and increased villi number and length in irradiated mice. Translocation of gut bacteria to spleen, liver and kidney were controlled in irradiated mice pretreated with melatonin. Radiation-induced gastrointestinal DNA strand breaks, lipid peroxidation, and expression of proapoptotic-p53, Bax, and antiapoptotic-Bcl-xL proteins were reversed in melatonin pretreated mice. This increase of Bcl-xL was associated with the decrease of Bax/Bcl-xL ratio. ABTS and DPPH radical assays revealed that melatonin treatment alleviated total antioxidant capacity in hematopoietic and gastrointestinal tissues. Present study demonstrated that melatonin pretreatment was able to prevent hematopoietic, immunological, and gastrointestinal radiation-induced injury, therefore, overcoming lethality in mice. These results suggest potential of melatonin in developing radioprotector for protection of bone marrow, spleen, and gastrointestine in planned radiation exposure scenarios including radiotherapy. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 501-518, 2017.
authors.affiliation: Division of Radiation Biodosimetry, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S. K. Mazumdar Marg, Timarpur, Delhi, 110054, India.|Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia-a Central University, Moulana Mohammad Ali Jauhar Marg, New Delhi, 110025, India.
authors.forename: Shahanshah
authors.initials: S
authors.lastname: Khan
authors.affiliation: Division of Radiation Biodosimetry, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S. K. Mazumdar Marg, Timarpur, Delhi, 110054, India.
authors.forename: Jawahar Singh
authors.initials: JS
authors.lastname: Adhikari
authors.affiliation: Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia-a Central University, Moulana Mohammad Ali Jauhar Marg, New Delhi, 110025, India.
authors.forename: Moshahid Alam
authors.initials: MA
authors.lastname: Rizvi
authors.affiliation: Division of Radiation Biodosimetry, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S. K. Mazumdar Marg, Timarpur, Delhi, 110054, India.
authors.forename: Nabo Kumar
authors.initials: NK
authors.lastname: Chaudhury
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D005720:Gamma Rays; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology / Q000528:radiation effects; D016130:Immunophenotyping; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003037:Cobalt Radioisotopes; D011837:Radiation-Protective Agents; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D008550:Melatonin
keywords: DNA strands breaks; HPSCs; T cells subpopulation; apoptosis; bacterial translocation; crypt regeneration; lipid peroxidation; melatonin; pro-versus-antiapoptotic proteins; γ-irradiation