title: Impairment of 8-iso-PGF(2ALPHA) isoprostane metabolism by dietary conjugated linoleic acid (CLA).
abstract: 8-iso-PGF(2alpha) isoprostane (IP) is one of the most-used markers of lipid peroxidation in experimental models and humans. After its formation, it is promptly metabolized to 2,3 dinor (DIN) in peroxisomes. Conjugated linoleic acid (CLA) is preferentially beta-oxidized in peroxisomes which may compete with IP, and thereby may affect its metabolism. In order to verify whether CLA is able to influence IP formation and/or metabolism and to explain the mechanism, we challenged rats supplemented with CLA or with triolein (as a control fatty acid), with a single dose of carbon tetrachloride (CCl(4)) or of bacterial lipopolysaccharide (LPS). The results showed that IP and its precursor arachidonic acid hydroperoxide, as well as malondialdehyde (MDA), increase significantly in the liver of rats challenged with CCl(4), irrespective of the diet, while in LPS-treated rats only nitrites in liver and isoprostane in plasma increase. On the other hand, the peroxisomal beta-oxidation products of IP, the DIN, is significantly lower in the CLA group with respect to control and triolein groups. To further investigate whether this is due to competition between CLA and IP at the cellular level, we incubated human fibroblasts from healthy subjects or patients with adrenoleukodystrophy (ALD), with CLA and/or commercially available IP. The rationale of this approach is based on the deficient peroxisomal beta-oxidation of fibroblasts from ALD patients, leading to a reduced formation of DIN. In both normal and ALD cells, the presence of CLA significantly inhibits the formation of DIN from IP. We may conclude that both in vitro and in vivo studies strongly suggest that CLA may impair IP catabolism in peroxisomes. Consequently an increase of IP, as a sole result of CLA intake, cannot be considered as a marker of lipid peroxidation.
authors.affiliation: Università degli Studi di Modena e Reggio Emilia, Dipartimento di Scienze Biomediche, Via Campi 287, 41100 Modena, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Iannone
authors.forename: Anna
authors.initials: A
authors.lastname: Petroni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Murru
authors.forename: Lina
authors.initials: L
authors.lastname: Cordeddu
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Carta
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Melis
authors.forename: Stefania
authors.initials: S
authors.lastname: Bergamini
authors.forename: Lara Della
authors.initials: LD
authors.lastname: Casa
authors.forename: Laura
authors.initials: L
authors.lastname: Cappiello
authors.forename: Romina
authors.initials: R
authors.lastname: Carissimi
authors.forename: Marianne
authors.initials: M
authors.lastname: O'Shea
authors.forename: Doris
authors.initials: D
authors.lastname: Bell
authors.forename: Enrico
authors.initials: E
authors.lastname: De Santis
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Banni
mesh_terms: D000326:Adrenoleukodystrophy / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020675:Peroxisomes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014304:Triolein / Q000494:pharmacology
chemical_list: C411579:2,3-dinor-5,6-dihydro-8-iso-prostaglandin F2(alpha); D004041:Dietary Fats; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; D014304:Triolein; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D015237:Dinoprost; D002251:Carbon Tetrachloride