title: Radioprotection of sensitive rat tissues by oligoelements Se, Zn, Mn plus Lachesis muta venom.
abstract: In this study we first evaluated the general radioprotective efficacy of Se, Zn and Mn (4 µg/ml each) plus Lachesis muta venom (4 ng/ml) combination (O-LM) by determining survival on rats irradiated with lethal doses of gamma-rays. The aim of the second part of the study was to investigate the O-LM ability to prevent ionizing radiation-induced damage on small intestine, bone marrow and submandibular glands. Hence, histological characteristics and functional studies, together with proliferation and apoptotic marker levels on whole body irradiated rats with a 5 Gy dose were evaluated. Results show that all animals of the untreated group died after whole body irradiation with 8 and 10 Gy while 60 day-survival was more than 80% and 40% in O-LM-treated animals, respectively. Histopathological examinations revealed a high degree of small intestine and submandibular gland radioprotection 3 days post-irradiation. O-LM inhibited histological damage on small intestine, restoring the radiation-induced reduction in villous height and crypt number. O-LM prevented radiation-induced loss of salivary gland function and morphological alterations. These effects were associated to a complete inhibition of radiation-induced apoptosis. Furthermore, studies performed 30 days post-irradiation revealed that O-LM significantly improved bone marrow repopulation, increasing all medullar progenies to the extent of the non-irradiated animals, and completely prevented permanent submandibular gland alterations. 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 conclude that O-LM is a non-toxic promising approach to achieve radioprotection for patients undergoing radiotherapy.
authors.affiliation: Institute of Immunooncology, University of Buenos Aires, Argentina.
authors.forename: Ernesto J V
authors.initials: EJ
authors.lastname: Crescenti
authors.forename: Vanina A
authors.initials: VA
authors.lastname: Medina
authors.forename: Máximo
authors.initials: M
authors.lastname: Croci
authors.forename: Lorena A
authors.initials: LA
authors.lastname: Sambuco
authors.forename: Juan P
authors.initials: JP
authors.lastname: Prestifilippo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Elverdin
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Bergoc
authors.forename: Elena S
authors.initials: ES
authors.lastname: Rivera
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001853:Bone Marrow / Q000187:drug effects / Q000293:injuries / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003435:Crotalid Venoms / Q000008:administration & dosage / Q000494:pharmacology; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000293:injuries / Q000528:radiation effects; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology; D013363:Submandibular Gland / Q000187:drug effects / Q000293:injuries / Q000528:radiation effects; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D003435:Crotalid Venoms; C072644:Lachesis venom; D011837:Radiation-Protective Agents; D008345:Manganese; D012643:Selenium; D015032:Zinc