Asian Pacifc Journal of Cancer Prevention, Vol 11, 2010 1015 Embelin Protection Against DEN and CCl 4 Induced Preneoplasia and Toxicity in Rat Liver Asian Pacifc J Cancer Prev, 11, 1015-1020 Introduction Numerous epidemiological studies have shown high dietary intake of fruits and vegetables, containing phytochemicals such as carotenoids, antioxidative vitamins, phenolic compounds, flavones, terpenoids, steroids, isothiocyanates, indoles and fbres have been reported for reduction in cancer risk or prevent multistage carcinogenesis (Singletery et al., 2000; Nishino et al., 2005). Embelin (2,5-dihydroxy-3-undecyl-1,4 - benzoquinone) is a naturally occurring alkyl benzoquinone, the active principle in the fruits of Embelia tsjeriam-cottam (syn. E. robusta) belonging to family Myrsinaceae. Fruits are used extensively in Ayurvedic system of medicine for the treatment of various diseases such as gastrointestinal disorders, dyspepsia, bronchitis, asthma, anaemia and skin diseases (Kirtikar and Basu, 1984; Sharma et al., 2002). Polyherbal formulations containing fruits of Embelia have been reported for treatment of various liver diseases like jaundice (Patki et al., 1990; Kothavade et al., 1996). Embelin has been shown to possess antihelminthic, analgesic, anti-infammatory, antipyretic, wound healing and contraceptive properties (Gupta et al. 1977; Gupta et 1 Department of Biological Sciences, Ramnarain Ruia College, Matunga, 2 Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, India. *For correspondence: drradhikapoojari@ gmail.com Abstract Embelin, an active constituent isolated from the fruits of Embelia tsjeriam–cottam was investigated for its chemopreventive and hepatoprotective effects against N-nitrosodiethylamine (NDEA) induced liver preneoplasia or carbon tetrachloride (CCl 4 ) induced liver damage. Rats received NDEA, 1ppm/g b.w. in drinking water for 6 weeks or CCl 4 , 0.7ml/kg i.p. once a week for 4 weeks and embelin 50mg, 100mg/kg b.w. orally prior, during and after exposure to NDEA/CCl 4 for 20 or 5 weeks, respectively. Embelin treatment signifcantly prevented NDEA or CCl 4 induced increase in biochemical marker enzymes: glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase, γ-glutamyl transpeptidase, glutathione-S-transferase, lipid peroxidase as well as hypoproteinemia, hypoalbuminuria and glutathione depletion. This was further substantiated by marked decrease in incidence of preneoplastic foci, and infammatory cells on histopathological and transmission electron microscopic analysis. The present study suggests embelin is a promising chemopreventive and hepatoprotective agent. Keywords: Embelin - chemoprevention - N-nitrosodiethylamine - hepatoprotective - carbon tetrachloride RESEARCH COMMUNICATION Chemopreventive and Hepatoprotective Effects of Embelin on N-Nitrosodiethylamine and Carbon Tetrachloride Induced Preneoplasia and Toxicity in Rat Liver Radhika Poojari 1* , Sanjay Gupta 2 , Girish Maru 2 , Bharat Khade 2 , Sanjay Bhagwat 1 al., 1991; Kumara et al 2007). Earlier reports have shown Embelin to possess antiproliferative activity in vitro, regression of fibrosarcoma in rats and chemopreventive activity against DENA induced hepatocarcinogenesis in Wistar rats based on preliminary liver function enzymes. The preneoplastic hepatic foci have been as end point models in assessing the toxic effects of hepatocarcinogens. Preneoplastic lesions have no obvious neoplastic nature, but have a high probability of progressing to a benign or malignant tumor in response to tumor promoters (Bannas ch, 1986; Cameron, 1989). In the present study we evaluated chemopreventive and hepatoprotective effects of Embelin isolated from fruits of E. tsjeriam-cottam in N-nitrosodiethylamine (NDEA) induced preneoplastic hepatic foci and cCarbon tetrachloride (CCl4) induced liver damage in rat model and correlated for the frst time biochemical alterations, antioxidant activity with histopathological changes and ultrastructural studies. Materials and Methods Isolation of Embelin The fruits of Embelia tsjeriam-cottam were authenticated