Preclinical report 885 Impact of naringenin on glycoprotein levels in N-methyl-N 0 -nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats Ganapathy Ekambaram, Peramaiyan Rajendran, Rajasekaran Devaraja, Raju Muthuvel and Dhanapal Sakthisekaran We have studied the chemopreventive role of naringenin against experimental gastric carcinogenesis in male Wistar rats. The animals were divided into five groups and six animals were included in each group. Stomach, liver, sera and kidney specimens were collected in the 20th week and the level of glycoproteins namely, hexose, hexosamine, sialic acid and fucose, were measured in the control, gastric cancer-induced, cancer naringenin pretreated, cancer naringenin posttreated and naringenin alone animals. The glycoprotein levels were increased in the gastric cancer-induced rats when compared with the control rats. The levels of glycoprotein were decreased significantly in cancer-bearing rats supplemented with naringenin as compared with the gastric cancer-induced rats. The result shows the gastroprotective effect of naringenin and describes the likelihood of naringenin in maintaining the integrity of cell membranes and gastric mucosa against oxidative damage. Moreover, we hypothesize that regulation of glycoprotein levels by naringenin could be associated with the regression of N-methyl-N 0 -nitro-N-nitrosoguanidine-induced gastric carcinoma. Anti-Cancer Drugs 19:885–890  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Anti-Cancer Drugs 2008, 19:885–890 Keywords: gastric cancer, glycoproteins, naringenin, N-methyl-N 0 -nitro-N-nitrosoguanidine, oxidative damage, rats Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India Correspondence to Professor Dhanapal Sakthisekaran, MSc, MPhil, PhD, Department of Medical Biochemistry, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India Tel: +91 44 2454 7091; fax: +91 44 2454 0709; e-mail: g_ekambaram@yahoo.co.in Received 29 January 2008 Revised form accepted 29 June 2008 Introduction Gastric cancer ranks as the second most common (10.4%) cause of cancer deaths worldwide [1,2]. Owing to its high incidence, marked attention is being given to prevent gastric cancer at the earliest possible stage. Experimental evidence suggests that sodium chloride could markedly augment the carcinogenic effects of N-methyl-N 0 -nitro-N-nitrosoguanidine (MNNG) in the glandular stomach [3]. Sodium chloride decreases the viscosity of gastric mucin and disconcerts the mucosal integrity. Although a high salt diet decreases the amount of glandular mucin (which acts against Helicobacter pylori infection), recent experimental data suggest that salt could increase the risk of stomach cancer by several folds [4]. Glycoproteins (GPs) play a crucial role in the main- tenance of cellular phenomena during cancerous trans- formation. GP levels are high in tumour tissues because of increased lipid peroxidation, which results in lowered antioxidant status [5], aberrant glycosylation [6] and increased lysosomal hydrolases and proteases [7]. It is widely believed that the carbohydrate moieties of GPs notably hexose, hexosamine, fucose and sialic acid have an important role in protein stability and functions [8]. Glycosidase distribution in serum has been documented in mammalian systems [9,10]. GPs are frequently used as diagnostic and prognostic markers of squamous cell carcinoma [11]. Elevated levels of glycosidases may occur in fibroblasts that are transformed by oncogenic viruses [12]. Of the various modern approaches undertaken to curtail the incidence of cancer, chemoprevention has been in the limelight in recent years. Fruits, vegetables and herbal beverages with diverse pharmacological properties have been found to possess a myriad of cancer prevention potentials [13–17]. It is widely believed that carcinogen- esis can effectively be kept at bay by the ingestion of certain plant-derived foods rich in flavonoids [18–21]. Naringenin, a natural flavanone of citrus fruits, has a plethora of pharmacological properties, that is, anti- carcinogenic, antimutagenic, anti-inflammatory and anti- atherogenic potentials [22–26]. Recent evidence suggests that naringenin can effectively scavenge free radicals and reactive oxygen species both in vivo and in vitro [27]. Therefore, we have measured GPs as a measure of gastric carcinogenesis and determined the role of naringenin against MNNG-induced gastric carcinogenesis in experi- mental rats. 0959-4973  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/CAD.0b013e32830ea1bc Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.