Arch Pharm Res Vol 31, No 6, 794-797, 2008 DOI 10.1007/s12272-001-1228-z 794 http://apr.psk.or.kr Chemoprotective Effects of Hesperidin Against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells Amirhosein Ahmadi 1 , Seyed Jalal Hosseinimehr 2,3 , Farshad Naghshvar 4 , Ebrahim Hajir 1 , and Mehran Ghahremani 4 1 Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran, 2 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran, 3 Pharmacetical Research Center, Mazandaran University of Medical Sciences, Sari, Iran, and 4 Department of Pathology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran (Received Arpil 3, 2008; Revised April 29, 2008; Accepted May 13, 2008) The preventive effect of hesperidin as a flavonoid was investigated in mouse bone marrow cells against genotoxicty induced by cyclophosphamide. Mice were orally (gavages) pre- treated with solutions of hesperidin at four different doses (50, 100, 200, and 400 mg/kg b.w.) for five consecutive days. Mice were injected intraperitoneally on the fifth day with cyclophos- phamide (50 mg/kg b.w.) and killed after 24 h for the evaluation of micronucleated polychro- matic erythrocytes (MnPCEs) and the ratio of PCE/(PCE+NCE) (polychromatic erythrocyte/ polychromatic erythrocyte + normochromatic erythrocyte). Three last doses of hesperidin sig- nificantly reduced frequency of MnPCEs induced by cyclophosphamide (p<0.0001). Hesper- din at dose 200 mg/kg b.w. reduced MnPCEs 2.37 time and also completely normalized PCE/ (PCE+NCE) ratio. Histological examination of bone marrow showed that hesperidin affected on proliferation and hyper cellularity of immature myeloid elements in bone marrow that reduced by cyclophsopahmide. It is obvious that hesperidin, may with antioxidative activity, reduced the oxidative stress and genotoxicity induced by cyclophosphamide in mouse bone marrow cells. Key words: Hesperidin, Genotoxicity, Micronucleus, Cyclophosphamide INTRODUCTION There are many reports that the hazardous environmental chemical capable induces genotoxic and carcinogenic effects on the mammary. The main mechanism is produc- ing of species free radical that induces damage to critical macromolecules such as DNA to promote chronic diseases such as cancers (Tiwari, 2001; Sporn, 1993). Although human body is equipped with self defense mechanisms such as detoxification process through various enzymes, serious exposure to dangerous chemicals can lead to mutagenic and carcinogenic events. Many natural com- pounds in plants have been reported to have potential antimutagenic or anticarcinogenic effects (Edenharder et al.,1998). Flavonoids and phenolic compounds have many biological properties, including hepatoprotective, antibac- terial and anticancer activities (Tiwari, 2001). Recently we reported that citrus extract had a significant protective effect on genotoxicity induced by gamma irradiation and cyclo- phosphamide (Hosseinimehr et al., 2003; Hosseinimehr and Karami, 2005). Hesperidin is a flavonone glycoside, belonging to the flavonoid family. This natural product is found in citrus species. Hesperidin was reported to have many biological effects including anti-inflammatory, anti- microbial, anticarcinogenic, antioxidant effects, and de- creasing capillary fragility (Garg et al., 2001). Recently we showed that hesperidin reduced genotoxicty induced by gamma irradiation in mouse bone marrow cells when administrated prior gamma irradiation (Hosseinimehr and Nemati, 2006). Cyclophosphamide (CP) induce DNA-DNA and DNA-protein crosslinks and it has shown chromosome damage, sister chromatid exchange as well as other genotoxic effects. It is a widely used and well document- ed reference genotoxic compound (Frank et al., 2005; Hosseinimehr et al., 2008). In this study, the antigenotoxic Correspondence to: Seyed Jalal Hosseinimehr, Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran Univer- sity of Medical Sciences, Sari, Iran Tel & Fax: 98-151-3261244 E-mail: sjhosseinim@yahoo.com, sjhosseinim@mazums.ac.ir