title: Ellagic acid modulates antioxidant status, ornithine decarboxylase expression, and aberrant crypt foci progression in 1,2-dimethylhydrazine-instigated colon preneoplastic lesions in rats.
abstract: Chemoprevention offers a novel approach to control the incidence of colorectal cancer (CRC), which is a fatal cause of malignancies in both Western and Asia countries. Ornithine decarboxylase (ODC) functions as a cell transition factor by regulating the biosynthesis of polyamines, which, allied with aberrant crypt foci (ACF) proliferation, cause early lesions of CRC. This study exemplifies the chemopreventive efficacy of ellagic acid (EA) in 1,2-dimethylhydrazine (DMH) initiated CRC in rats. Subcutaneous injection of DMH (40 mg/kg body weight twice a week for 2 weeks) to the rats resulted in elevated expression of ODC, a genetic marker for CRC, and its transcription factor myelocytomatosis oncogene (c-myc). Furthermore, increased levels of lipid peroxidation and hydroperoxides with diminished levels of antioxidants including superoxide dismutase, catalase, and reduced glutathione were also observed in the tissues of DMH-intoxicated rats. Oral supplementation of EA significantly influences maintenance of antioxidant status and transcriptional inactivation of ODC expression, reducing ACF proliferation and/or progression, thus signifying the chemopreventive efficacy of EA against CRC.
authors.affiliation: Department of Biochemistry, School of Life Sciences, Maraimalai (Guindy) campus, University of Madras, Chennai, Tamilnadu, India. kasinathan.nirmalkumar@gmail.com
authors.forename: Kasinathan Nirmal
authors.initials: KN
authors.lastname: Kumar
authors.forename: Subramaniya Bharathi
authors.initials: SB
authors.lastname: Raja
authors.forename: Natarajan
authors.initials: N
authors.lastname: Vidhya
authors.forename: Sivachithamparam Niranjali
authors.initials: SN
authors.lastname: Devaraj
mesh_terms: D019813:1,2-Dimethylhydrazine; D058739:Aberrant Crypt Foci / Q000473:pathology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000032:analysis*; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000737:chemistry* / Q000473:pathology; D004610:Ellagic Acid / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011230:Precancerous Conditions / Q000737:chemistry / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D004610:Ellagic Acid; D009955:Ornithine Decarboxylase; D019813:1,2-Dimethylhydrazine