title: Attenuation of DMBA/croton oil induced mouse skin papilloma by Apodytes dimidiata mediated by its antioxidant and antimutagenic potential.
abstract: Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity. Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF). Materials and methods Antimutagenic potential of AMF (25, 50 and 75 μg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250 mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC-MS. Results AMF (75 μg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250 mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC-MS. Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential.
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Menon K
authors.initials: MK
authors.lastname: Divya
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Sasidharan
authors.initials: S
authors.lastname: Salini
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Nair
authors.initials: N
authors.lastname: Meera
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lincy
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Menon
authors.initials: M
authors.lastname: Seema
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Achuthan C
authors.initials: AC
authors.lastname: Raghavamenon
authors.affiliation: a Department of Biochemistry , Amala Cancer Research Centre, Amala Nagar (Recognized Research Centre - University of Calicut) , Thrissur , Kerala , India.
authors.forename: Thekkekara D
authors.initials: TD
authors.lastname: Babu
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology; D016587:Antimutagenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003436:Croton Oil; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000378:metabolism; D019684:Magnoliopsida / Q000737:chemistry; D008297:Male; D000432:Methanol / Q000737:chemistry; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012969:Sodium Fluoride / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D000975:Antioxidants; D010936:Plant Extracts; D012997:Solvents; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D012969:Sodium Fluoride; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000432:Methanol
keywords: Chemoprevention; mutation; oxidative stress; phytoconstituents; skin tumourigenesis