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Human & Experimental Toxicology
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Inhibition of radiation-induced clastogenicity by Aegle marmelos (L.) Correa in mice bone marrow exposed to different doses of {gamma}-radiation

G.C. Jagetia

Department of Radiobiology, Kasturba Medical College, Manipal-576 104, India, gc.jagetia{at}gmail.com

P. Venkatesh

Department of Radiobiology, Kasturba Medical College, Manipal-576 104, India

The frequency of micronucleated polychromatic (MPCE), normochromatic erythrocytes (MNCE), and polychromatic/normochromatic erythrocyte ratio (PCE/NCE), was studied in the bone marrow of mice orally administered with 0, 200, 225, 250, 275 and 300 mg/kg body weight of hydroalcoholic leaf extract of Aegle marmelos (AME). Treatment of mice with AME, once daily for 5 consecutive days, before exposure to 2 Gy resulted in a significant decline in the frequency of MPCE when compared to the non-drug-treated irradiated control. The greatest reduction in MPCE was observed for 250 mg/kg body weight AME, accompanied by the highest polychromatic erythrocyte to normochromatic erythrocyte ratio, in comparison with the non-drug-treated irradiated control. Therefore, further studies were carried out using this dose of AME, where the animals were administered with 250 mg/kg body weight of AME before exposure to 0, 0.5, 1, 2, 3 and 4 Gy of {gamma}-radiation and evaluated at 12, 24, 36 and 48 hours post-irradiation. Whole body irradiation of mice to different doses of {gamma}-radiation resulted in a dose-dependent increase in the frequency of MPCE at all post-irradiation times. Treatment of 250 mg/kg AME orally (p.o.) before irradiation significantly reduced the frequency of MPCE at all post-treatment times. The frequency of MPCE increased with time, reached a peak level at 24 hours, and declined thereafter. The occurrence of MNCE has also shown a pattern similar to MPCE, except that the MNCE frequency reached a peak level by 48 hours. The AME significantly reduced the frequency of MNCE at all post-irradiation times, when compared to the non-drug-treated irradiated group. Treatment of mice with AME before exposure to different doses of {gamma}-radiation resulted in the inhibition of a radiation-induced decline in the PCE/NCE ratio, when compared with the concurrent irradiated controls. To gain insight into the mechanism of action, AME was tested for its antioxidant effects in cell-free chemical systems using H2O 2/FeSO4 to generate hydroxyl ({whitebullet}OH) radicals, which were measured by a fluorescent probe, 2V, 7V-dichlorofluorescin diacetate (DCFH/DA). Xanthine/xanthine oxidase was used to generate superoxide (O2{whitebullet}-) anion radical, which was measured by a fluorescent probe dihydroethidium (DHE). AME significantly reduced fluorescence in a concentration dependent manner, indicating its efficacy to scavenge free radicals. Our results demonstrate that one of the mechanism of reduction in the radiation-induced DNA damage in mice bone marrow by AME may be due to scavenging of free radicals and elevation in the antioxidant status, as previously reported. Human & Experimental Toxicology (2007) 26, 111-124

Key Words: Aegle marmelos • antioxidant • free radical scavenging • fluorescence • micronuclei • radiation

Human & Experimental Toxicology, Vol. 26, No. 2, 111-124 (2007)
DOI: 10.1177/0960327107071867


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