Inhibition of radiation-induced clastogenicity by Aegle marmelos (L.) Correa in mice bone marrow exposed to different doses of γ-radiation

Abstract

<jats:p> 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 γ-radiation and evaluated at 12, 24, 36 and 48 hours post-irradiation. Whole body irradiation of mice to different doses of γ-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 γ-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 H<jats:sub>2</jats:sub>O<jats:sub> 2</jats:sub>/FeSO<jats:sub>4</jats:sub> to generate hydroxyl (<jats:sup>◦</jats:sup>OH) radicals, which were measured by a fluorescent probe, 2V, 7V-dichlorofluorescin diacetate (DCFH/DA). Xanthine/xanthine oxidase was used to <jats:sub>generate superoxide (O2</jats:sub><jats:sup>◦-</jats:sup><jats:sub>) anion radical, which was</jats:sub> 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 &amp; Experimental Toxicology (2007) 26, 111-124 </jats:p>

Aegle marmelos (L.) Correa (Bael) and Its Phytochemicals in the Treatment and Prevention of Cancer

“…Additionally, preclinical studies have also confirmed that the Bael leaf extract has a high margin of drug safety and does not possess systemic, teratogenic, or genotoxic effects at optimal protective concentrations. 35,40,66,67 When these observations are considered along with its beneficial effects in the prevention and treatment of cancer, it is safe to assume that Bael remains a species with tremendous potential but only when the lacunae in the existing knowledge are bridged. The outcomes of such studies may be useful for the clinical applications of Bael in humans and may open up a new therapeutic avenue.…”

“…38 The leaf extract prevented radiation clastogenesis in the cultured human peripheral blood lymphocytes and the bone marrow cells of mice, indicating its effectiveness as an antimutagen. 39,40 The phytochemical eugenol 41 is also reported to possess radioprotective effects and its presence in the extract may have contributed to these results.…”

Therapeutic potential of Aegle marmelos (L.)-An overview

“…Recently, Abdullakasim et al have observed that A. marmelos fruit drink had high quantities of total phenolic compounds and was a good antioxidant [31] . A. marmelos leaf extract reduced radiation-induced DNA damage in cultured human peripheral blood lymphocytes and in mouse bone-marrow cells, indicating that A. marmelos is an efficient anticlastogen [32] . Transitional metals like iron, undergo redox cycling, resulting in production of ROS.…”

Effect of Extraction Solvent on the Phytoconstituents of <i>Aegle marmelos</i> (L.) Correa

“…Petroleum ether extract contains fats and fixed oil while aqueous extract contains amino acids, tannins (condensed and pseudo tannins) and starch [5]. IR has been reported to possess various pharmacological actions, mainly antidiabetic [6], antiinflammatory [7], nephroprotective [8], antibacterial [9], antioxidant and antimicrobial activity [10]. Further, the principle constituents of IR such as sinapic and ferulic acids have exhibited behavioural and pharmacological…”

“…The bark as well as fruit is reputed to be a valuable Ayurvedic medicine for dysentery and various intestinal complaints [3,4]. It possesses potentmicrofilarial [5], radio protective [6], analgesic [7], antihyperglycemic, antidyslipidemic [8], anticancer [9,10] and antidiabetic activity [11,12]. Solvent extraction is most frequently used technique for isolation of plant metabolites.…”