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: Liliana M Bivol, Rolf K Berge, Bjarne M Iversen
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 294 Issue 2 Pg. R438-47 (Feb 2008) ISSN: 0363-6119 [Print] United States
• PMID: 18032469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl2 protein, rat
• Chemokine CCL2
• Free Radical Scavengers
• Interleukin-1beta
• Interleukin-6
• NF-kappa B p50 Subunit
• Nitrates
• Nitrites
• Reactive Oxygen Species
• Sodium, Dietary
• Sulfides
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• 8-epi-prostaglandin F2alpha
• Nitric Oxide
• 1-(carboxymethylthio)tetradecane
• Dinoprost

Topics

• Animals
• Body Weight
• Chemokine CCL2 (blood)
• Dinoprost (analogs & derivatives, urine)
• Disease Models, Animal
• Eating
• Free Radical Scavengers (pharmacology)
• Hypertension, Renal (drug therapy, metabolism)
• Interleukin-1beta (blood)
• Interleukin-6 (blood)
• Kidney Cortex (metabolism)
• Male
• NF-kappa B p50 Subunit (metabolism)
• Nephritis (drug therapy, immunology, prevention & control)
• Nitrates (blood)
• Nitric Oxide (metabolism)
• Nitrites (blood)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Sodium, Dietary (pharmacology)
• Sulfides (pharmacology)
• Surgical Instruments
• Transcription Factor RelA (metabolism)
• Tumor Necrosis Factor-alpha (blood)