title: Gastroprotective Mechanisms of the Monoterpene 1,8-Cineole (Eucalyptol).
abstract: Recently, our research group identified and reported 1,8-cineole (CIN), a monoterpene that naturally occur in many aromatic plants, as one of the major constituent of the essential oil from leaves of Hyptis martiusii (EOHM), as well as characterized the gastroprotective action of this oil. The aim of this study was to investigate the mechanisms of action involved in the antiulcer and healing activity of CIN, in order to confirm its correlation with the gastroprotective effect of EOHM. Wistar rats were exposed to different protocols (acute ulceration, gastrointestinal motility and antisecretory activity). In addition, were determinated the involvement of nitric oxide and sulphydryl groups; the levels of gastric mucus, lipid peroxidation, sulphydryl groups and myeloperoxidase activity. The healing ability was evaluated by acetic acid-induced chronic ulcer and histological and immunohistochemical analysis (PCNA, Ki-67 and BrdU). The treatment with CIN inhibited ethanol-, ethanol/HCl- and indomethacin-induced gastric lesions. The highest doses of CIN inhibited gastric emptying, but did not affect intestinal transit. CIN (100 mg/kg) reduced the volume of basal but not stimulated acid secretion. CIN increased levels of mucus (89.3%), prevented depletion of -SH groups (62.6%) and reduced the level of lipid peroxidation (55.3%) and myeloperoxidase activity (59.4%) in the gastric mucosa. In chronic ulcer model, CIN reduced in 43.1% the gastric area lesion, promoted significant regeneration and restoration of the levels of mucus in glandular cells as confirmed by histological analysis; and promoted increase in cell proliferation as evidenced by reactivity for PCNA, Ki-67 and BrdU. This findings demonstrate the role of 1,8-cineole as an important ulcer healing agent and indicate the involvement of antioxidant and cytoprotective mechanisms in the gastroprotective effect of compound. This study also provides evidence that 1,8-cineole is related to the gastroprotective effect of the essential oil of Hyptis martiusii.
authors.affiliation: Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil.
authors.forename: Germana Freire
authors.initials: GF
authors.lastname: Rocha Caldas
authors.affiliation: Department of Physiology and Pharmacology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Alisson Rodrigo da Silva
authors.initials: AR
authors.lastname: Oliveira
authors.affiliation: Department of Physiology and Pharmacology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Alice Valença
authors.initials: AV
authors.lastname: Araújo
authors.affiliation: Department of Physiology and Pharmacology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Simone Sette Lopes
authors.initials: SS
authors.lastname: Lafayette
authors.affiliation: Department of Histology and Embryology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Giwellington Silva
authors.initials: GS
authors.lastname: Albuquerque
authors.affiliation: Department of Histology and Embryology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Jacinto da Costa
authors.initials: Jda C
authors.lastname: Silva-Neto
authors.affiliation: Department of Physical Education and Sport Sciences, Universidade Federal de Pernambuco, 55608-680, Vitória de Santo Antão, PE, Brazil.
authors.forename: João Henrique
authors.initials: JH
authors.lastname: Costa-Silva
authors.affiliation: Department of Physiology and Pharmacology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Ferreira
authors.affiliation: Department of Biological Chemistry, Universidade Regional do Cariri, 63105-000, Crato, CE, Brazil.
authors.forename: José Galberto Martins da
authors.initials: JG
authors.lastname: Costa
authors.affiliation: Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco, 50740-521, Recife, PE, Brazil; Department of Physiology and Pharmacology, Universidade Federal de Pernambuco, 50670-901, Recife, PE, Brazil.
authors.forename: Almir Gonçalves
authors.initials: AG
authors.lastname: Wanderley
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000032:analysis; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D000077591:Eucalyptol; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D031331:Hyptis / Q000737:chemistry; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D009093:Mucus / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000517:prevention & control*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003511:Cyclohexanols; D005765:Gastrointestinal Agents; D019394:Ki-67 Antigen; D039821:Monoterpenes; D018809:Proliferating Cell Nuclear Antigen; D020011:Protective Agents; D013438:Sulfhydryl Compounds; D001973:Bromodeoxyuridine; D000077591:Eucalyptol