title: Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension.
abstract: ANG II promotes inflammation through nuclear factor-kappaB (NF-kappaB)-mediated induction of cytokines and reactive oxygen species (ROS). The aim of the present study was to examine the effect of tetradecylthioacetic acid (TTA), a modified fatty acid, on NF-kappaB, proinflammatory markers, ROS, and nitric oxide (NO) production in two-kidney, one-clip (2K1C) hypertension. The 2K1C TTA-treated group had lower blood pressure (128 +/- 3 mmHg) compared with 2K1C nontreated (178 +/- 5 mmHg, P < 0.001). The p50 and p65 subunits of NF-kappaB were higher in the clipped kidney (0.44 +/- 0.01 and 0.22 +/- 0.01, respectively) compared with controls (0.25 +/- 0.03 and 0.12 +/- 0.02, respectively, P < 0.001). In the 2K1C TTA-treated group, these values were similar to control levels. The same pattern of response was seen in the nonclipped kidney. In 2K1C hypertension, cytokines plasma were higher than in control: TNF-alpha was 13.5 +/- 2 pg/ml (P < 0.03), IL-1beta was 58.8 +/- 10 pg/ml (P = 0.003), IL-6 was 210 +/- 33 pg/ml (P < 0.001), and monocyte chemoattractant protein-1 was 429 +/- 21 pg/ml (P = 0.04). In the 2K1C TTA-treated group, these values were similar to controls, and the same pattern was seen in the clipped kidney. Clipping increased 8-iso-PGF-2alpha (P < 0.01) and decreased NO production (P < 0.01 vs. control) in the urine. TTA treatment normalized these values. NO production was also lower in clipped and nonclipped kidney (P < 0.001). After TTA treatment, these values were similar to controls. The results indicate that TTA has a potent anti-inflammatory effect in 2K1C by inhibition of p50/p65 NF-kappaB subunit activation, reduction of cytokines production and ROS, and enhanced NO production.
authors.affiliation: Renal Research Group, Institute of Medicine, Haukeland Hospital, Bergen, Norway. monica.bivol@med.uib.no
authors.forename: Liliana M
authors.initials: LM
authors.lastname: Bivol
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.forename: Bjarne M
authors.initials: BM
authors.lastname: Iversen
mesh_terms: D000818:Animals; D001835:Body Weight; D018932:Chemokine CCL2 / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004195:Disease Models, Animal; D004435:Eating; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009393:Nephritis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012982:Sodium, Dietary / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology*; D013525:Surgical Instruments; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016166:Free Radical Scavengers; D053583:Interleukin-1beta; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D012982:Sodium, Dietary; D013440:Sulfides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; C062078:1-(carboxymethylthio)tetradecane; D015237:Dinoprost