title: Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis.
abstract: Xenobiotic metabolizing enzymes are chief determinants in both the susceptibility to mutagenic effect of chemical carcinogens and in the response of tumors to chemotherapy. The present study was aimed to analyze the effect of geraniol administration on the activity of phase I and phase II carcinogen metabolizing enzymes through the nuclear factor erythroid 2-related factor-2 (Nrf2) activation against 4-niroquinoline-1-oxide (4NQO) induced oral carcinogenesis. The well-known chemical carcinogen 4NQO (50 ppm) was used to induce oral carcinogenesis through drinking water for 4, 12, and 20 weeks. The degree of cancer progression at each stage was confirmed by histological examination. At the end of the experimental period, 100% tumor formation was observed in the oral cavity of 4NQO induced animals with significant (P<0.05) alteration in the status of tumor markers, tongue and liver phase I and phase II drug metabolizing enzymes indicating progression of disease. Oral administration of geraniol at the dose of 200 mg/kg b.wt., thrice a week to 4NQO induced animals was able to inhibit tumor formation and thereby delayed the progression of oral carcinogenesis by modulating tongue and liver phase I and phase II drug metabolizing enzymes, as substantiated further by the histological and transmission electron microscopic studies. Our results demonstrate that geraniol exerts its chemopreventive potential by altering activities of phases I and II drug metabolizing enzymes to achieve minimum bioactivation of carcinogen and maximum detoxification.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamilnadu, India.
authors.forename: Arumugam
authors.initials: A
authors.lastname: Madankumar
authors.forename: Subramaniyan
authors.initials: S
authors.lastname: Jayakumar
authors.forename: Krishnan
authors.initials: K
authors.lastname: Gokuladhas
authors.forename: Balan
authors.initials: B
authors.lastname: Rajan
authors.forename: Subramanian
authors.initials: S
authors.lastname: Raghunandhakumar
authors.forename: Selvamani
authors.initials: S
authors.lastname: Asokkumar
authors.forename: Thiruvengadam
authors.initials: T
authors.lastname: Devaki
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000080462:Acyclic Monoterpenes; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control / Q000648:ultrastructure
chemical_list: D000080462:Acyclic Monoterpenes; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013729:Terpenes; D015112:4-Nitroquinoline-1-oxide; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C007836:geraniol