title: Isomer-specific effects of conjugated linoleic acid on lipid peroxidation in humans: regulation by alpha-tocopherol and cyclo-oxygenase-2 inhibitor.
abstract: We have found previously that supplementation with conjugated linoleic acid (CLA) induces lipid peroxidation and inflammation in humans as indicated by an increase of 8-iso-prostaglandin F2alpha (PGF2alpha) and 15-keto-dihydro-PGF2alpha respectively. The present study was undertaken firstly to study the regulatory mechanisms behind these effects, and secondly to see if these effects are specific to different isomers of CLA. Sixty healthy men and women, divided into six groups, were given a cyclo-oxygenase (COX)-2 inhibitor (rofecoxib; 12 mg/day), alpha-tocopherol (200 mg/day) or neither treatment (control group) over a period of 6 weeks. During the last 4 weeks, three groups were given a CLA preparation (3.5 g/day) mainly containing the isomers cis-9, trans-11 and trans-10, cis-12 (CLA mix), and the three other groups a CLA preparation mainly containing the isomer trans-10, cis-12 (CLA 1012; 4.0 g/day). Treatment with alpha-tocopherol or COX-2 inhibitor did not alter the basal urinary levels of either 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha. Both CLA preparations induced an increase in 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha in the urine, with a larger increase being found in the CLA 1012 group. Treatment with the COX-2 inhibitor suppressed the increase in urinary 15-keto-dihydro-PGF2alpha in the CLA 1012 group, but not in the CLA mix group. Neither the COX-2 inhibitor nor alpha-tocopherol had any effect on 8-iso-PGF2alpha levels after supplementation with CLA. The CLA-induced production of PGF2alpha metabolites is probably partially mediated by COX-2. Levels of the induced lipid peroxidation may be dependent on the isomeric property of CLA.
authors.affiliation: Unit for Clinical Nutrition Research, Department for Public Health and Caring Sciences/Geriatrics, Uppsala University, PO Box 609, S-751 25 Uppsala, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Smedman
authors.forename: Bengt
authors.initials: B
authors.lastname: Vessby
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
mesh_terms: D000328:Adult; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D007536:Isomerism; D019787:Linoleic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D028441:F2-Isoprostanes; D007527:Isoenzymes; D008565:Membrane Proteins; C075750:8-epi-prostaglandin F2alpha; C026528:15-ketoprostaglandin F2alpha; D019787:Linoleic Acid; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D024502:alpha-Tocopherol