Despite the excellent chemotherapeutic effect of irinotecan, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. This study was carried out to find whether propolis preparations and related flavonoids (quercetin, naringin) might enhance irinotecan-induced cytotoxicity to tumor cells in mice bearing Ehrlich ascites tumors (EAT) while protecting normal blood, liver, and kidney cells. The preparation of propolis and their flavonoids were given to mice intraperitoneally at a dose of 100 mg kg(-1) body weight for three consecutive days before the ip injection of EAT cells (2×10(6)). Irinotecan was administered ip at dose of 50 mg kg(-1) on days 3, 4, and 5 after tumor cell inoculation. The combination treatment resulted in substantial inhibition of the growth of EAT cells as well as treatment with quercetin or irinotecan alone, whereas other treatment by itself showed little effect. However, when mice were pre-treated with test components prior to irinotecan, the frequencies of irinotecan-induced micronuclei (MN) was decreased but in mice bearing tumor QU and EEP increased number of micronucleated cells. Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells.

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The radioprotective effects of propolis and polyphenolic compounds from propolis on the radiation-induced mortality of mice exposed to 9 Gy of g g-irradiation were studied. Intraperitoneal (i.p.) treatment of mice at doses of 100 mg kg ؊1 body weight of propolis (water or ethanolic extract; WSDP or EEP) or its polyphenolic compounds (quercetin, naringin caffeic acid, chrysin) consecutively for 3 d before irradiation, delayed the onset of mortality and reduced the symptoms of radiation sickness. All test compounds provided protection against hematopoietic death (death within 30 d after irradiation). The greatest protection was achieved with quercetin; the number of survivors at the termination of the experiment was 63%. According to statistical analyses by the Kaplan-Meier method and the log-rank test, a significant difference between test components and control was found (pϽ0.001). Treatment with test components after lethal irradiation was ineffective. These results suggest that propolis and its polyphenolic compounds given to mice before irradiation protect mice from the lethal effects of whole-body irradiation.

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...

The aim of this study was to assess radioprotective effects of quercetin and the ethanolic extract of propolis (EEP) in CBA mice exposed to a single radiation dose 4 Gy ( 60 Co). The mice were treated with 100 mg kg -1 quercetin or EEP a day for three consecutive days either before (pre-treatment) or after gamma-irradiation (therapy). Leukocyte count was determined in blood drawn from the tail vein, and DNA damage in leukocytes was assessed using the alkaline comet assay. Genotoxic effects of the test compunds were also evaluated in non-irradiated mice. The levels of radioprotection provided by both test compounds were compared with those established in mice that were given chemical radioprotector S-(2-Aminoethyl)isothiouronium bromide hydrobromide (AET). Mice that received pre-treatment were less sensitive to irradiation. Mice given the post-irradiation therapy showed a slight but not signifi cant increase in total leukocyte count over irradiated negative control. Quercetin showed better protective properties than EEP in both pre-treatment and therapy, and activated a higher number of leukocytes in non-irradiated mice. The alkaline comet assay suggests that both natural compounds, especially when given as pre-treatment, protect against primary leukocyte DNA damage in mice. At tested concentrations, EEP and quercetin were not genotoxic to non-irradiated mice. AET, however, caused a slight but not signifi cant increase in DNA damage. Although the results of this study show the radioprotective potential of the test compounds, further investigation is needed to clarify the underlying protection mechanisms.