496CHEMOPREVENTIVE AND THERAPEUTIC EFFECT OF CAPSAICIN AGAINST DIETHYLNITROSAMINE INDUCED LIVER INJURY AND HEPATOCELLULARCARCINOMA IN RATSHepatocellular carcinoma (HCC) is the second most frequent cause of death in 2010 throughout the world. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Capsaicin, a homovanillic acid derivative and spicy component of hot chili pepper has been shown to possess antioxidant, anti-inflammatory and chemopreventive properties. Our study was designed to investigate the hepatoprotective and therapeutic effect of capsaicin using a two-stage model of rat liver carcinogenesis initiated with DENA and promoted by Phenobarbital. Hepatocarcinogenesis was induced by single intraperitoneal injection of DENA (200mg/kg). After 2 weeks, the rats were given PB (0.05% in drinking water) for 14 successive weeks. During the last 4 days, PB was withdrawn from the drinking water. Capsaicin treatment (2.5 mg/Kg b.wt. in DMSO orally) was started 5 weeks prior to the initiation and continued for 21weeks in preventive group, while in therapeutic group rats treated for 5 weeks after HCC induction. Administration of DENA and PB caused significant elevation in serum (ALT, AST and ALP) activities, MDA and NOlevels,it significantly decreased ALB and cytochrome clevel. Also, it depleted the antioxidant activities of GSH and GST. In preventive group treatment with capsaicin restored the levels of liver markers near to normal, significantly decreased MDA level and increased NO level thereby confirming hepatoprotective effect by increasing oxidative stress and induced apoptosis by significant increase of cytochrome c level. While, in therapeutic group capsaicin decreased NO and MDA levels and increased GSH and GST activities. A section of liver was also subjected to histopathological analysis that confirmed our results. It is suggested that capsaicin suppress DEN- induced hepatocarcinogenesis and could be developed as a promising chemopreventive natural supplement for liver cancer. Also, improves biochemical markers in therapeutic groupdr_fzahran@yhoo.comResearch582014Hepatocellular carcinoma (HCC),Capsaicin,DENA,Phenobarbital,cytochrome cFaten Z. Mohammed,Ahmed S. Sultan,Al-shimaa M. AbasBiochemistry Department, Faculty of Science, Zagazig University, Egypt, Biochemistry Department, Faculty of Science, Alexandria University, Egypt,Biochemistry Department, Faculty of Science, Zagazig University, Egypt