Redox metal chelation ameliorates radiation-induced bone marrow toxicity in a mouse model.
Since zinc desferrioxamine (Zn-DFO) has been shown to be a very potent protector against injuries induced by redox-active metal ions, we examined its protective effect against radiation-induced toxicity. We found that treatment with Zn-DFO given before TBI increased the survival of mice irradiated with 7.5 and 8.5 Gy. Zn-DFO also protected against radiation-induced myelosuppression and body weight loss, while soluble Il6 levels in serum were normalized in mice pretreated with Zn-DFO. We concluded that administration of Zn-DFO prior to TBI protected BALB/c mice from radiation-induced toxicity, increasing survival rates by up to 75%. The biological effect of Zn-DFO is known to result from its effect on the production of intracellular hydroxyl free radicals mediated by redox-active metal ions, and both metal chelation and zinc delivery appear to be equally likely mechanisms for this outcome. We suggest that radiation-induced toxicity is caused by the deleterious effect of redox-active metal ions, and that compounds which modulate this redox activity may act as radioprotectors.
Nagler
R M
RM
Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Eichen
Y
Y
Nagler
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D002614:Chelating Agents / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology; D014916:Whole-Body Irradiation; D015032:Zinc
D002614:Chelating Agents; D015850:Interleukin-6; D011837:Radiation-Protective Agents; D003676:Deferoxamine; D015032:Zinc