title: Distribution and immune responses resulting from oral administration of D-limonene in rats.
abstract: We investigated the relationship between the absorptive pathway and the immune responses of the lung, particularly the phagocytic function of alveolar macrophages (Mphi) after oral administration of D-limonene in rats. D-Limonene was orally administered in oily solution with a stomach tube in thoracic duct-cannulated rats, and the lymphatic output of D-limonene was measured. D-Limonene levels reached a maximum in thoracic duct lymph and lung 3 h after its oral administration. It also significantly increased in bronchoalveolar lavage fluid (BALF) and alveolar Mphi, in which there was frequently a focal exudation of lipid droplets containing D-limonene into the alveolar cavity through alveolar capillary walls. Second, D-limonene orally given to rats (250, 500, 1,000 mg/kg/d) for 8 consecutive days resulted in a marked increase in both the number and the phagocytic activity of alveolar Mphi compared to the controls. BALF from rats dosed with D-limonene (1,000 mg/kg/d) enhanced the phagocytic activity of alveolar Mphi from control rats because the dose was prolonged. The activity of alveolar Mphi following in vitro incubation with D-limonene also increased in a dose-dependent manner. An oral administration of D-limonene enhanced the Con A-stimulated proliferation of splenocytes. These results suggest that D-limonene taken up from the thoracic duct lymph moves to the lung and directly activates the immune response of alveolar MO there, or indirectly activates it through activated lymphocytes.
authors.affiliation: Department of Nutrition, School of Medicine, The University of Tokushima, Japan. hamada@nutr.med.tokushima-u.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Hamada
authors.forename: Kayoko
authors.initials: K
authors.lastname: Uezu
authors.forename: Junko
authors.initials: J
authors.lastname: Matsushita
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kishino
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D008401:Gas Chromatography-Mass Spectrometry; D000077222:Limonene; D008168:Lung / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D010587:Phagocytosis / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D013729:Terpenes / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D013897:Thoracic Duct / Q000378:metabolism
chemical_list: D053138:Cyclohexenes; D013729:Terpenes; D000077222:Limonene