Protection of cellular DNA from gamma-radiation-induced damages and enhancement in DNA repair by troxerutin.
The effect of troxerutin on gamma-radiation-induced DNA strand breaks in different tissues of mice in vivo and formations of the micronuclei were studied in human peripheral blood lymphocytes ex vivo and mice blood reticulocytes in vivo. Treatments with 1 mM troxerutin significantly inhibited the micronuclei induction in the human lymphocytes. Troxerutin protected the human peripheral blood leucocytes from radiation-induced DNA strand breaks in a concentration dependent manner under ex vivo condition of irradiation (2 Gy). Intraperitoneal administration of troxerutin (175 mg/kg body weight) to mice before and after whole body radiation exposure inhibited micronuclei formation in blood reticulocytes significantly. The administration of different doses (75, 125 and 175 mg/kg body weight) of troxerutin 1 h prior to 4 Gy gamma-radiation exposure showed dose-dependent decrease in the yield of DNA strand breaks in murine blood leucocytes and bone marrow cells. The dose-dependent protection was more pronounced in bone marrow cells than in blood leucocytes. Administration of 175 mg/kg body weight of the drug (i.p.) 1 h prior or immediately after whole body irradiation of mice showed that the decrease in strand breaks depended on the post-irradiation interval at which the analysis was done. The observed time-dependent decrease in the DNA strand breaks could be attributed to enhanced DNA repair in troxerutin administered animals. Thus in addition to anti-erythrocytic, anti-thrombic, fibrinolytic and oedema-protective rheological activity, troxerutin offers protection against gamma-radiation-induced micronuclei formation and DNA strand breaks and enhances repair of radiation-induced DNA strand breaks.
Maurya
Dharmendra Kumar
DK
Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, 400085, India.
Balakrishnan
Sreedevi
S
Salvi
Veena Prakash
VP
Nair
Cherupally Krishnan Krishnan
CK
D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D020552:Comet Assay; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008875:Middle Aged; D014916:Whole-Body Irradiation
D006896:Hydroxyethylrutoside; C005865:troxerutin; D004247:DNA