Radiation Protectors: the Unexpected Benefits

Grdina, David J.; Sigdestad, Curtis P.

doi:10.3109/03602538908994143

Cited by 54 publications

(14 citation statements)

References 75 publications

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“…Scavenging and elimination of free radical species constitute the main mechanism of radioprotection by several of these compounds, as they remove and detoxify products of water radiolysis and reactive oxygen species (ROS), before these toxic substances interact with critical macromolecules such as DNA [34]. Unfortunately, most of chemical radioprotectors (AET, WR 2721, and WR 1065) have shown toxic side effects that limit their use in medical practice [35]. Investigations for effective and nontoxic compounds with radioprotecting ability led to increasing interest in naturally occurring antioxidants.…”

Section: Discussionmentioning

confidence: 99%

Radioprotective Effects of Gallic Acid in Mice

Nair

2013

BioMed Research International

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Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100 mg/kg body weight), one hour prior to whole body gamma radiation exposure (2–8 Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control).

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Section: Discussionmentioning

confidence: 99%

Radioprotective Effects of Gallic Acid in Mice

Nair

2013

BioMed Research International

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“…10,14,18 Laboratory data suggest that the mechanism of amifostine's selective protection is related to its preferential uptake in normal vs malignant tissues. 13,19 This is in part due to the better vascularity, higher alkaline phosphatase levels (required for dephosphorylation of the prodrug to its active metabolite -the free thiol WR-1065), and the higher pH of normal tissue.…”

Section: Discussionmentioning

confidence: 99%

Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation

Spencer

Horvath

Gibson

et al. 2005

Bone Marrow Transplant

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Summary:In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n ¼ 43) or not receive (n ¼ 47) amifostine 910 mg/m 2 prior to melphalan 200 mg/m 2 . Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65% of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P ¼ 0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P ¼ 0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14% of the amifostine and control groups, respectively (P ¼ 0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to highdose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis. Bone Marrow Transplantation (2005) 35, 971-977.

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“…Unfortunately, most of chemical radioprotectors (AET, WR 2721, WR 1065) have shown toxic side effects that limit their use in medical practice. 4) Investigations for effective and non toxic compounds with radioprotection capability led to increasing interest in naturally occurring antioxidants.…”

mentioning

confidence: 99%

Evaluation of the Radioprotective Effects of Propolis and Flavonoids in Gamma-Irradiated Mice: The Alkaline Comet Assay Study

Benković

Oršolić

Knežević

et al. 2008

Biological & Pharmaceutical Bulletin

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Ionizing radiation is classified as a potent carcinogen. When interacting with living cells, it causes a variety of changes depending on exposed and absorbed dose, duration of exposure and interval after exposure, and susceptibility of tissues.1) It is well established that ionizing radiation by direct ionization and through generation of toxic free radicals causes single strand breaks, double strand breaks, oxidative damage to sugar and base residues, chromosomal aberration and mutation. 2)Since the radiation effects are not discriminate, transient and/or permanent injury to normal tissues and cells are unavoidable.3) Efforts to reduce toxicity to normal tissue cells and organs have led to the search for cytoprotective agents. Unfortunately, most of chemical radioprotectors (AET, WR 2721, WR 1065) have shown toxic side effects that limit their use in medical practice. 4) Investigations for effective and non toxic compounds with radioprotection capability led to increasing interest in naturally occurring antioxidants.Propolis is adhesive resinous substance manufactured by honey bees from leaf, bud and sap of trees and flower blossoms. Major constituents of propolis are flavonoids, organic acids, phenols, various kinds of enzymes, vitamins and minerals.5,6) Because of its broad spectrum of biological properties the interest in propolis as harmless medicine has been increased.7) Propolis and its active substances flavonoids showed antibacterial, 7) analgesic/anti-inflammatory, 7) antioxidant, 6) prooxidant, 8) immunoenchancement, 9) antiproliferative activity in cultured human tumor cells 10) and antitumor activity in mice.11) Antioxidant activity of flavonoids is based on ability of direct free radicals scavenging or stabilizing the reactive oxygen species (ROS) by interacting with the reactive compound of the radical. Because of the high reactivity of the hydroxyl substituents of the flavonoids, radicals are made inactive. 7) ROS in the presence of iron resulted in lipid peroxidation. Some flavonoids are known to chelate iron. 7)Flavonoids can also increase the function of the endogenous antioxidant enzyme systems; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and gluthation.12) Furthermore, antioxidant effects may be a result of a combination of radical scavenging and an interaction with enzyme functions.Genotoxicity of ionizing radiation was studied with different approaches using sensitive methods to measure a single and double strand breaks (SSB, DSB) of DNA; mostly used tests are comet assay for SSB and micronucleus test for DSB.The aim of this study was to evaluate radioprotective effects of propolis and single flavonoids, caffeic acid, chrysin and naringin in the whole-body irradiated (WBI) mice with two doses of g-irradiation using an alkaline comet assay. The efficiency of tested compounds was evaluated on the white blood cells of mice treated preventively and therapeutically. The possible genotoxic effects of all compounds were also assessed on non...

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Radiation Protectors: the Unexpected Benefits

Cited by 54 publications

References 75 publications

Radioprotective Effects of Gallic Acid in Mice

Radioprotective Effects of Gallic Acid in Mice

Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation

Evaluation of the Radioprotective Effects of Propolis and Flavonoids in Gamma-Irradiated Mice: The Alkaline Comet Assay Study

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