Radioprotection by mangiferin in DBAxC₅₇BL mice: a preliminary study

Abstract

The radioprotective effects of various concentrations (0, 0.25, 0.5, 1, 2, 5, 10, 17.5, 25, 50, 75 and 100 mg/kg b.wt.) of mangiferin (MGN) was studied in the DBAxC₅₇BL mice whole body exposed to 10 Gy of γ-irradiation. Treatment of mice with different doses of MGN, one hour before irradiation reduced the symptoms of radiation sickness and delayed the onset of mortality when compared with the non-drug treated irradiated controls. The radioprotective action of MGN increased in a dose dependent manner up to 2 mg/kg and declined thereafter. The highest radioprotective effect was observed at 2 mg/kg MGN, where greatest number of animals survived against the radiation-induced mortality. The administration of 0.5, 1, 2, 5, 10 and 17.5 mg/kg MGN reduced the radiation-induced gastrointestinal death as evident by a greater number of survivors up to 10 days in this group when compared with the DDW+10 Gy irradiation group. A similar effect of MGN was observed for the radiation-induced bone marrow deaths also. Our study demonstrates that mangiferin, a gluosylxanthone, present in the Mangifera indica protected mice against the radiation-induced sickness and mortality and the optimum protective dose of 2 mg/kg was 1/200 of LD₅₀ dose (400 mg/kg) of MGN. The administration of 400 mg/kg MGN induced 50% mortality, therefore LD₅₀ of the drug was considered to be 400 mg/kg.

Introduction

The observation by Patt et al. (1949) that pretreatment of rats with cysteine protected them against the X-ray-induced mortality opened a new field of research in Radiation Biology. Subsequently, several chemical compounds were synthesized and tested for their radioprotective applicability and the sulphydryl compounds were found to be good radioprotectors. However, the practical ability of majority of thiol compounds remained limited, due to their high systemic toxicity at the optimum protective doses (Sweeney, 1979). The high toxicity of thiols compounds necessitated search for alternative agents, which could be less toxic and highly effective at non-toxic doses. It was also thought that products/compounds isolated from natural sources could be of substantial use as non-toxic radioprotectors. Therefore, investigators diverted their attention towards the plant/natural products during the last decade and a half. Certain antioxidant phytochemical compounds like ascorbic acid, β-carotene, vitamin E, curcumin, caffeine, chlorogenic acid, vitamin A, bixin, polyphenols and flavonoids have been reported to protect mice against the radiation-induced damage in different study systems (Redpath et al., 1982; Sarma and Kesavan, 1993; Abraham et al., 1993; Thresiamma et al., 1996; Harapanhalli et al., 1994; Shimoi et al., 1994, Shimoi et al., 1996, Shimoi et al., 1997; George et al., 1999; Uma Devi et al., 1998, Uma Devi et al., 1999, Uma Devi et al., 2000; Jagetia and Reddy, 2002).

Mangifera indica, commonly known as mango, is consumed worldwide as a fruit, culinary and flavoring agent. The fruits, barks and leaves of M. indica have been reported to possess diverse medicinal properties in the traditional Indian system of medicine, the Ayurveda, and are widely used in several medicinal preparations (Nadkarni, 1976; Sairam et al., 2003). The plant has been reported to contain antiviral, antibacterial, antihyperglycaemic, analgesic, antiinflammatory, antidiarrhoeal, antiamoebic, spasmolytic, immunostimulant and immunomodulatory properties (Zhu et al., 1993; Aderibigbe et al., 1999; Yoosook et al., 2000; Makare et al., 2001; Garrido et al., 2001; Nkuo-Akenji et al., 2001; Garcia et al., 2002; Tona et al., 1998, Tona et al., 2000; Sairam et al., 2003). The extract of M. indica has been reported to be an antioxidant and a potent scavenger of hydroxyl radicals and hypochlorous acid. It has also been found to chelate iron, inhibit lipid peroxidation and DNA damage in vitro (Scartezzini and Speroni, 2000; Martinez et al., 2000, Martinez et al., 2001).

Mangiferin, a glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-beta-D-glucoside) isolated from M. indica, has been reported to be chemopreventive, antidiabetic, antineoplastic, antiviral and antihyperlipidemic in type 2 diabetes (Guha, et al., 1996; Yoshikawa, et al., 2001; Miura, et al., 2001). Mangiferin has been reported to reduce TPA-induced free radical production and DNA fragmentation in hepatic and brain cells of mice (Sato et al., 1992). It has also been reported to protect against the cardiac and renal damage in rats (Muruganandan et al., 2002).

The lessons from the experience with radioprotectors world wide are that the animal studies using death of the irradiated animals as the end point is the most confirmatory, because the 30 days time period after lethal whole body irradiation clearly indicates the capacity of the drug, in test to modulate the recovery and regeneration of the gastrointestinal epithelium and the hemopoietic progenitor cells in the bone marrow, the two most radiosensitive organs that are essential for sustenance of life. The diverse medicinal properties of mangiferin stimulated us to investigate its radioprotective activity. Therefore, the present study was undertaken to obtain an insight into the radioprotective effect of mangiferin, a glucosylxanthone in mice exposed to 10 Gy of ⁶⁰Co gamma irradiation.