title: Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys.
abstract: The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from (60)Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg(-1)) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg(-1) protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg(-1), and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg(-1). Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys.
authors.affiliation: State Scientific Center Russian Federation - Institute of Biomedical Problems, Russian Academy of Science, 76a Khoroshovskoe schuss, Moscow 123007, Russia mikhail-v-vasin@yandex.ru.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Vasin
authors.affiliation: Scientific Institute of Medical Primatology, Russian Academy of Medical Science, 1 Veseloe, Sochi 354376, Russia.
authors.forename: Leonid F
authors.initials: LF
authors.lastname: Semenov
authors.affiliation: Center of Chemistry of Medicinal Agents, 7 Zuvovskaia Street, Moscow 119815, Russia.
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Suvorov
authors.affiliation: State Scientific Center Russian Federation - Institute of Biomedical Problems, Russian Academy of Science, 76a Khoroshovskoe schuss, Moscow 123007, Russia.
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Antipov
authors.affiliation: State Scientific Center Russian Federation - Institute of Biomedical Problems, Russian Academy of Science, 76a Khoroshovskoe schuss, Moscow 123007, Russia.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Ushakov
authors.affiliation: Burnazian Federal Medical Biophysical Center, Federal Biomedical Agency, 17a Gamalea Street, Moscow 123098, Russia.
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Ilyin
authors.affiliation: Scientific Institute of Medical Primatology, Russian Academy of Medical Science, 1 Veseloe, Sochi 354376, Russia.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Lapin
mesh_terms: D054508:Acute Radiation Syndrome / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D008253:Macaca mulatta; D008297:Male; D010636:Phenols / Q000008:administration & dosage*; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*
chemical_list: D010636:Phenols; D011837:Radiation-Protective Agents; C086896:indralin
keywords: acute radiation syndrome; haemorrhagic syndrome; monkeys; radioprotectors; indralin