Melatonin attenuates 60Co γ‐ray‐induced hematopoietic, immunological and gastrointestinal injuries in C57BL/6 male mice

• Published in: Environmental toxicology Vol. 32; no. 2; pp. 501 - 518
• Main Authors: Khan, Shahanshah, Adhikari, Jawahar Singh, Rizvi, Moshahid Alam, Chaudhury, Nabo Kumar
• Format: Journal Article
• Language: English
• Published: 01-02-2017
• Subjects: apoptosis; bacterial translocation; crypt regeneration; DNA strands breaks; HPSCs; lipid peroxidation; melatonin; pro‐versus‐antiapoptotic proteins; T cells subpopulation; γ‐irradiation
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22254

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 using 60Co‐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.