title: Asiatic acid attenuates pre-neoplastic lesions, oxidative stress, biotransforming enzymes and histopathological alterations in 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis.
abstract: Asiatic acid (AA), a pentacyclic triterpenoid, derived from the tropical medicinal plant Centella asiatica is known to exhibit numerous pharmacological properties. We hypothesized that AA will have chemopreventive potential against 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male Wistar rats. Rats were arbitrarily divided into six groups. Group I rats were processed as control. Group II rats received AA (8 mg/kg b.w., p.o.) and groups III-VI rats received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups IV-VI rats received AA at the doses of 2, 4 and 8 mg/kg b.w., respectively, for 16 weeks. Our results discovered that supplementation with AA to the DMH-exposed rats significantly decreased the incidence of polyps and Aberrant crypt foci (ACF) as compared to the DMH-alone-exposed rats. Moreover, in the AA-supplemented DMH-exposed rats, we ascertained increased activities of the antioxidants and decreased levels of lipid peroxidation (LPO) in the liver and circulation and enhanced levels of both LPO and antioxidants in the colon, which were altered in the DMH-alone-exposed rats. Furthermore, we also observed altered activities of vitamins C and E and biotransforming enzymes in DMH-alone-exposed rats, which were reversed on AA supplementation. All the observations were supported by our histological findings. Thus, we can conclude that, AA could be used as an effective chemopreventive agent against DMH-induced colon carcinogenesis.
authors.affiliation: a Department of Biochemistry and Biotechnology, Faculty of Science , Annamalai University , Annamalainagar , India.
authors.forename: Aktarul Islam
authors.initials: AI
authors.lastname: Siddique
authors.affiliation: a Department of Biochemistry and Biotechnology, Faculty of Science , Annamalai University , Annamalainagar , India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Mani
authors.affiliation: a Department of Biochemistry and Biotechnology, Faculty of Science , Annamalai University , Annamalainagar , India.
authors.forename: Sivaranjani
authors.initials: S
authors.lastname: Arivalagan
authors.affiliation: a Department of Biochemistry and Biotechnology, Faculty of Science , Annamalai University , Annamalainagar , India.
authors.forename: Nisha Susan
authors.initials: NS
authors.lastname: Thomas
authors.affiliation: a Department of Biochemistry and Biotechnology, Faculty of Science , Annamalai University , Annamalainagar , India.
authors.forename: Nalini
authors.initials: N
authors.lastname: Namasivayam
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000493:pharmacokinetics; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D001711:Biotransformation; D002374:Catalase / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D053978:Pentacyclic Triterpenes; D014810:Vitamin E; C017032:asiatic acid; D002374:Catalase; D013482:Superoxide Dismutase; D019813:1,2-Dimethylhydrazine; D001205:Ascorbic Acid
keywords: 1,2-Dimethylhydrazine; Albino Wistar rats; Asiatic acid; chemoprevention; colon cancer; oxidative stress