Radioprotective potential of a novel therapeutic formulation of oligoelements Se, Zn, Mn plus Lachesis muta venom.
In this study we evaluated in vivo the tolerance induced by the combination of Se, Zn and Mn (4 microg/ml each) plus Lachesis muta venom (4 ng/ml) (O-LM) to high doses of ionizing radiation. The protective effect of O-LM was investigated on the small-intestine and bone marrow of mice irradiated with a single whole-body dose of 10 Gy employing a (137)Cs source. Mice were sacrificed 3 days after irradiation. Mice receiving a subcutaneous daily O-LM injection starting 30 days before irradiation, showed a higher number of crypts, enhanced villous conservation and lack of edema or vascular damage in comparison to the untreated and irradiated group. In addition, O-LM treatment decreased vascular damage and the grade of aplasia preserving medullar progenies induced by ionizing radiation on mouse bone marrow. The protective effect of O-LM against radiation injury to the small intestine was associated with an increase in proliferation and a reduction of apoptosis in intestinal crypts and furthermore, to an enhanced intestinal immunoreactivity of MnSOD, and CuZnSOD, and also catalase. Based on the present results and taking into account that O-LM is being safely administered in phase I clinical trial as an immunomodulator, we suggest that O-LM could be an attractive candidate as a safe radioprotective agent for patients undergoing radiotherapy.
Crescenti
Ernesto
E
Institute of Immunooncology, University of Buenos Aires, Buenos Aires, Argentina.
Croci
Máximo
M
Medina
Vanina
V
Sambuco
Lorena
L
Bergoc
Rosa
R
Rivera
Elena
E
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology* / Q000528:radiation effects*; D003435:Crotalid Venoms / Q000008:administration & dosage*; D004338:Drug Combinations; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D019216:Metals, Heavy / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D003435:Crotalid Venoms; D004338:Drug Combinations; C072644:Lachesis venom; D019216:Metals, Heavy; D011837:Radiation-Protective Agents