Radioprotective activity

Various other properties intestinal antiseptic (932, 933), fungicide (934, 935), insecticide (895. 898), coccidiostatic activity (936), car-cinolytic activity (937), radioprotective activity (938), antimutagenic activity (939, 940). 

A variety of other metals and their complexes have been studied for radioprotective activity. Among these are copper glycinate, strontium chloride, ZnNa -diethylenetriaminepentaacetate (ZnDTPA), and selenium, which has been studied because of its relationship to endogenous antioxidant mechanisms, especiaHy GSH peroxidase and vitamin E. 

Pentoxifylline is stmcturaHy related to other methylxanthine derivatives such as caffeine [58-02-2] (1,3,7-trimethylxanthine), theobromine [83-67-0] (3,7-dimethylxanthine), and theophylline [58-55-9] (3,7-dihydro-1,3-dimethyl-1 H-piirine-2,6-dione or 1,3-dimethylxanthine), which also show radioprotective activity in some instances, suggesting that methylxanthines as a dmg class may radioprotect through a common mechanism (see Alkaloids). In a retrospective analysis of cervical and endometrial cancer patients receiving primary or adjuvant XRT, no association between caffeine consumption and incidence of acute radiation effects has been found. However, there was a decreased incidence of severe late radiation injury in cervical cancer patients who consumed higher levels of caffeine at the time of thek XRT (121). The observed lack of correlation between caffeine consumption and acute radiation effects is consistent with laboratory investigations using pentoxifylline. 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

Interleukin-1 OC and (3. IL-1 has radioprotective activity toward BM and other tissues (151,164). IL-1 is produced in response to endotoxin, other cytokines, and microbial and viral agents, primarily by monocytes and macrophages. Other nucleated cells can also produce it. IL-1 appears to play an important role in the regulation of normal hemopoiesis directly by stimulating the most primitive stem cells and indirectly by stimulating other hemopoietic factors, including G-CSF, GM-CSF, M-CSF, and IL-6. 

Basic FGF can also stimulate murine hemopoietic progenitors in vitro. It is synergistic with hemopoietic growth factors such as GM-CSF, EPO, and Meg-CSF and has radioprotective activity in vivo, increasing the number of day-9 and day-12 CFU-S from lethaUy irradiated animals (195). Furthermore, b-FGF combiaed with GM-CSF protects against the killing of murine and human CFU-GM exposed to radiation in vitro (195). 

Endotoxin and Muramyl Dipeptide Derivatives. Bacterial cell wall constituents such as the Hpopolysaccharide endotoxin and muramyl dipeptide, which stimulate host defense systems, show radioprotective activity in animals (204). Although endotoxin is most effective when given - 24 h before irradiation, it provides some protection when adrninistered shortiy before and even after radiation exposure. Endotoxin s radioprotective activity is probably related to its Hpid component, and some of its properties may result from PG and leukotriene induction (204). 

The potential for normal brain tissue injury is one of the limiting factors in the use of XRT for brain tumors. Pentobarbital is a cerebral radioprotectant in rodent and primate models after single doses, but is associated with significant risks. Of alternative barbiturates, thiopental given to tats receiving 70-Gy (7000-rad) whole-brain irradiation in a single fraction enhances the 30-day survival similarly to pentobarbital, whereas ethohexital and phenobarbital show no radioprotective activity (250). 

Ohta, S., N. Sakurai, T. Inoue and M. Shinoda. Studieson chemical protectors against radiation. XXV. Radioprotective activities of various crude drugs. Yakugaku Zasshi 1987 107(1) 70-75. 

Selenodiazadihexylgermetane 151 offered weak radioprotective activity <2001MBD199, 2003AOM135>, while steroidal dithiaphosphetanthione 152 and its. S -dimcr were considered as promising antimicrobial agents <2003PS2003>. 

The radioprotective activity of several classes of organogermanium derivatives (germa-thiazolidines, germadithioacetals, germatranes and germylated sulfides) has been studied41,43,157-159. 

Germadithioacetals R1R2Ge[SCH(R3)CH2R4]2 have an important radioprotective activity (DRF 1.5-1.7)42,43,159-162. 

In in vivo experiments, the correlation between the radioprotecting activity and antiradical properties of synthetic antioxidants was determined [14, 15]. Kinetic studies on natural antioxidants - vitamins were carried out their constants as inhibitors of radical processes were determined [16, 17]. In the works by Khrapova et al., the chemiluminescence method adapted to studies on bioantioxidants in lipids was used with this method, the problems of synergism and anthagonism of synthetic and natural antioxidants were studied and the antioxidant system in membrane lipids was characterized as a whole [18]. 

Prabhakar KR, Veerapur VP, Parihar KV, Priyadarsini KI, Rao BSS, Unnikrishnan MK. (2006) Evaluation and optimization of radioprotective activity of Coronopus didymus Linn, in y-irradiated mice. Int JRadiat Biol 82 525-536. 

After these works, the intensive research in chemical radioprotection started by the synthesis of new compounds which will be efficient with lower toxicity. 5everal chemical products showed a fair radioprotective activity, especially sulphur compounds such as aminothiols, disulfides, phosphorothioates, thiazolidines, aminoethylisothiourea and dithiolanes. However, whereas these compounds have an interesting radioprotective activity. 

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