title: Essential fatty acid-deficient rats are resistant to oleic acid-induced pulmonary injury.
abstract: Because leukotrienes and prostaglandins are inflammatory mediators derived from arachidonic acid, their potential role in oleic acid-induced lung injury was evaluated in control and in essential fatty acid-deficient (EFAD) rats depleted of arachidonic acid substrate. In control rats, oleic acid (0.06 ml/kg iv) increased the pulmonary permeability index (measured by scintigraphy) from -10 +/- 13 x 10(-6) s-1 to 217 +/- 20 x 10(-6) s-1 and 118 +/- 13 x 10(-6) s-1 at 5 and 50 min (P less than 0.05), respectively. It also caused arterial hypoxemia at 30 min (P less than 0.05). Compared with saline controls, oleic acid increased bronchoalveolar lavage fluid levels of immunoreactive (i) LTC4/D4, iLTB4, (P less than 0.01), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) (P less than 0.05). In EFAD rats, oleic acid failed to significantly increase the lung permeability index at 5 and 50 min. In contrast to control rats, oleic acid failed to cause hypoxemia in the EFAD rats. Bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha after oleic acid in EFAD rats were lower compared with oleic acid controls, whereas iLTC4/D4 in the oleic acid EFAD group was not decreased. Treatment with intraperitoneal ethyl arachidonate (400 mg over 2 wk) reversed the resistance of EFAD rats such that the pulmonary edema (P less than 0.05) was evident after oleic acid. This latter group also manifested a significant (P less than 0.05) rise in the bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha. These results suggest that arachidonic acid metabolites contribute to oleic acid-induced pulmonary permeability.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston.
authors.forename: H A
authors.initials: HA
authors.lastname: Ball
authors.forename: J A
authors.initials: JA
authors.lastname: Cook
authors.forename: K M
authors.initials: KM
authors.lastname: Spicer
authors.forename: W C
authors.initials: WC
authors.lastname: Wise
authors.forename: P V
authors.initials: PV
authors.lastname: Halushka
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D005228:Fatty Acids, Essential / Q000172:deficiency*; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000032:analysis; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D055370:Lung Injury; D009829:Oleic Acids / Q000494:pharmacology*; D010539:Permeability; D010976:Platelet Count; D011863:Radioimmunoassay; D011877:Radionuclide Imaging; D051381:Rats; D013189:SRS-A / Q000032:analysis; D007507:Therapeutic Irrigation; D013997:Time Factors
chemical_list: D005228:Fatty Acids, Essential; D009829:Oleic Acids; D013189:SRS-A; D007975:Leukotriene B4