Radioprotective effect

Glutamine has been widely examined as a potential agent for enhancing intestinal repair foUowing radiation injury, although its value in this regard remains to be clearly estabHshed (144). Glutamine does exert radioprotective effects in cultured CHO ceUs. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

DC047 Shimoi, K., S. Masuda, B. Shen, M. Eurugori, and N. Kinae. Radioprotective effects of antioxidative plant flavanoids in mice. Mutat Res 1996 350(1) 153-161. 

Lorente, and M. Alcaraz. Radioprotective effects in vivo of phenolics extracted from Olea europaea L. leaves... 

Radioprotective effect. Rice seeds of cul-tivars Katakutara and Kusabue, kept in the seed hull and irradiated with y-radiation, showed greater germination than those that had been dehulled and irradiated ° . Salivary secretion. Decoction of the grain, administered intraperitoneally to mice at a dose of 100 mg/kg, was inactive vs pilocarpine-induced salivary flow in streptozo-tocin-diabetic mice " . ... 

In a related research, Storm et al. (1993) have reported a radioprotective effect of squalene. Mice were administrated by 2% squalene for 14 days before and 30 days after a lethal whole-body y-irradiation. Results showed that white cell counts in squalene-treated groups were considerably high when compared to nontreated control groups. Also, white cell protection was observed along a prolonged survival. Squalene treatment was suggested to exhibit cellular and systemic radioprotection as a result of this research. 

B23. Burlakova, E. B., and Dziuba, N. M., Synthetic inhibitors and natural antioxidants. II. The antioxidative activity of liver lipids of irradiated mice and die radioprotective effect of inhibitors of free radical reactions. Biofizika 11, 54—57 (1966). 

Adrien, L., Fatome, M., Laval, J.D., Rene, L., and Royer, R. 1976. Radioprotecting effects of A 3-chromenes substituted by an electron-attracting group in the 3-position. European Journal of Medicinal Chemistry, ll(l) 81-2. 

Ramadan, L.A., Roushdy, H.M., Abu-Senna, G.M., Amin, N.E., El-Deshw, O.A. Radioprotective effect of silymarin against radiation-induced hepatotoxicity. Pharmacol. Res. 2002 45 447-454... 

Studies of radioprotective effects of cimetidine have demonstrated reduced frequency of radiation-induced micronuclei and chromosomal aberrations at various doses in rat bone marrow cells. 

Hosseinimehr SJ,TavakoliH,PourheirdariG,Sobhani A,Shafiee A.Radioprotective effects of citrus extract agains gamma-irradiation in mouse bone marrow cells. J Radiat Res 2003 44 237-241. 

It is essential to establish certain criteria to evaluate the synthesized compounds, in particular their radioprotective effectiveness and their toxicity. For each of the molecules we synthesize, first we evaluate its acute (48 hours) and medium-term (2-30 days) toxicity in male Swiss CD1 mouse. The molecule is injected intraperitonally at different concentrations to determine the LD5o,ox/48h/ defined as the concentration which kills 50% ofthe animals at 48 hours. Then, radioprotective effectiveness is determined in the same animal model. In a preliminary study, the product is administered at the maximum tolerated dose (defined as 1/2 LD5otox/48h) 15 or 90 minutes before radiation exposure at doses LD,ooirr/3od nd LD,ooirr/3od + 2 Gy (LD,ooirr/3od is defined as the irradiation dose which kills 100% of the animals 30 days after exposure). Survival is observed for 30 days. In a second experiment we determine the Dose Reduction Factor (DRF) for the most radioprotective compounds. DRF is the ratio between the LDsoirr/sod of treated mice and that of non treated mice. 

WR-2721 (H2NCH2CH2CH2HNCH2CH2SPO3H2) is one of the best currently known radioprotectors. It was the subject of many studies because of its very high radioprotective effect [11-12]. In spite of some side effects (vomiting in 25% ofthe cases, hypotension, etc), WR-2721 is currently used for a clinical use, because it preferentially protects normal cells. The structure of these phosphorated derivatives is presented in Figure 5 ... 

Fatome M., Poutrain R, Granger R., Orzalesi H., Robbe Y., Randon M., Fernandez J.R, Radioprotective effects of thiazolidines, Chim.Then, 1970,5,312-317. 

Jagetia, G. C., Venkatesh, R, and Baliga, M. S. (2003). Evaluation of the radioprotective effect of Aegle marmelos (1.) Correa in cultured human peripheral blood lymphocytes exposed to different doses of gamma-radiation A micronucleus study. Mutagenesis 18, 387-393. 

The Cu-Zn-SOD-mimetic activity of Cu(II)(3,5-DIPS)2 and its lipid solubility were criteria used to select this complex in the initial attempt to study a copper complex as a radioprotectant. This complex was found to prevent death in 58% of the lethally irradiated (10 Gy, 0.4Gy/min) mice when they were thought to have been treated with 0.49 mmol/kg, 3 h before irradiation [505]. Subsequent studies revealed that this protection could be achieved with a much lower dose of complex suspended in a propyleneglycol-poly(vinyl alcohol)-saline vehicle. Treatment with 0.16 mmol/kg produced a 60% increase in survival in similarly irradiated and treated mice [506]. Most recent studies suggest that this radioprotectant effect may be achieved with a still further reduced dose of 0.04 mmol/kg and this lower dose appears to be as effective if given 3 h after irradiation as it is when given 3 h before irradiation. 

Using the same rationale as is used above in the purine section, it can be seen from the results in the Table that an extensive back reaction of the deoxyguanylic acid -(Cl2") radical occurs. The slight radioprotective effect of chloride in acidic solutions of deoxycytidylic acid and deoxyadenylic acid may be caused by the inability of these compounds to react with Cl2". 

Superoxide dismutases are able to protect cells from damaging effects caused by radiation 3i8-32o> reaction was proposed, in which SOD removes reactive oxygen species, generated by the irradiation and thus preventing the organisms from an attack by primary radicals or their reaction products, respectively Other reports on the radioprotective effect include the induction of superoxide dismutase in irradiated whole organs However, a radiation-induced SOD synthesis was not... 

Radioprotective effects of melatonin given intrape-ritoneally to male adult albino mice (10 mg/kg) became apparent in a significant reduction in micronuclei polychromatic erythrocytes when animals were treated with melatonin 1 h before and not... 

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