Radioprotection of normal tissues in tumor-bearing mice by troxerutin.
The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of gamma-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from gamma-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by ip one hour prior to 4 Gy whole-body gamma-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in gamma-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals.
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
Dharmendra Kumar
DK
Maurya
Veena Prakash
VP
Salvi
Cherupally Krishnan
CK
Krishnan Nair
D000818:Animals; D002462:Cell Membrane / Q000528:radiation effects*; D004247:DNA / Q000528:radiation effects* / Q000648:ultrastructure; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005354:Fibrosarcoma / Q000473:pathology / Q000532:radiotherapy*; D005720:Gamma Rays / Q000009:adverse effects / Q000627:therapeutic use; D006896:Hydroxyethylrutoside / Q000008:administration & dosage* / Q000031:analogs & derivatives; D007274:Injections, Intraperitoneal; D008099:Liver / Q000528:radiation effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000528:radiation effects*; D008928:Mitochondria / Q000528:radiation effects; D009928:Organ Specificity; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control*; D011835:Radiation Protection / Q000379:methods*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D051381:Rats; D013154:Spleen / Q000528:radiation effects
D006896:Hydroxyethylrutoside; D011837:Radiation-Protective Agents; C005865:troxerutin; D004247:DNA