title: Melanin, a promising radioprotector: mechanisms of actions in a mice model.
abstract: The radioprotective effect of extracellular melanin, a naturally occurring pigment, isolated from the fungus Gliocephalotrichum simplex was examined in BALB/C mice, and the probable mechanism of action was established. At an effective dose of 50mg/kg body weight, melanin exhibited both prophylactic and mitigative activities, increasing the 30-day survival of mice by 100% and 60%, respectively, after exposure to radiation (7Gy, whole body irradiation (WBI)). The protective activity of melanin was primarily due to inhibition of radiation-induced hematopoietic damages as evidenced by improvement in spleen parameters such as index, total cellularity, endogenous colony forming units, and maintenance of circulatory white blood cells and platelet counts. Melanin also reversed the radiation-induced decrease in ERK phosphorylation in splenic tissue, which may be the key feature in its radioprotective action. Additionally, our results indicated that the sustained activation of AKT, JNK and P38 proteins in splenic tissue of melanin pre-treated group may also play a secondary role. This was also supported by the fact that melanin could prevent apoptosis in splenic tissue by decreasing BAX/Bcl-XL ratio, and increasing the expressions of the proliferation markers (PCNA and Cyclin D1), compared to the radiation control group. Melanin also reduced the oxidative stress in hepatic tissue and abrogated immune imbalance by reducing the production of pro-inflammatory cytokines (IL6 and TNFα). In conclusion, our results confirmed that fungal melanin is a very effective radioprotector against WBI and the probable mechanisms of radioprotection are due to modulation in pro-survival (ERK) signaling, prevention of oxidative stress and immunomodulation.
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. amitbio@rediffmail.com
authors.forename: A
authors.initials: A
authors.lastname: Kunwar
authors.forename: B
authors.initials: B
authors.lastname: Adhikary
authors.forename: S
authors.initials: S
authors.lastname: Jayakumar
authors.forename: A
authors.initials: A
authors.lastname: Barik
authors.forename: S
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: S
authors.initials: S
authors.lastname: Raghukumar
authors.forename: K I
authors.initials: KI
authors.lastname: Priyadarsini
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004249:DNA Damage; D005720:Gamma Rays; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D006999:Hypocreales / Q000737:chemistry; D007109:Immunity / Q000187:drug effects / Q000528:radiation effects; D007202:Indicators and Reagents; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008543:Melanins / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents; D012996:Solutions; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013534:Survival
chemical_list: D007202:Indicators and Reagents; D008543:Melanins; D011837:Radiation-Protective Agents; D012996:Solutions; D051058:Oncogene Protein v-akt; D020928:Mitogen-Activated Protein Kinases