[Influence of ET-1 and ETA receptor blocker (BQ123) on the level of TNF-α in the brain rat]

Pol Merkur Lekarski. 2016 Jun;40(240):369-71.
[Article in Polish]

Abstract

Endothelin 1 (ET-1) in addition to the vasoconstriction, also has mitogenic, proinflammatory and proagregation activities. The mediators of inflammatory responses are cytokines, including special role attributed to tumor necrosis factor (TNF-α).

Aim: The aim of this study was to evaluate the effect of ET-1 and its receptor blocker (BQ123) on the level of TNF-α in the brain rat.

Materials and methods: Experiments were performed on four groups of Wistar-Kyoto rats. Animals were divided into four groups of 8 rats. Group I - control was administered into the tail vein solution of 0.9 % NaCl. Group II - saline followed by ET-1 (3 μg/kg b.w.). Group III - saline followed by BQ123 (1 mg/kg b.w.). Group IV (BQ123/ET-1) - BQ123 (1 mg/kg b.w.) administered 30 min before ET-1 (3 μg/kg b.w.).

Results: Administration of ET-1 at doses of 3 μg/kg b.w. resulted in a statistically significant increase in TNF-α concentrations in brain homogenates compared to the control group (p<0.01). Administration of the ET(A) receptor blocker - BQ123 (1mg/kg b.w.) 30 min before administration of ET-1 significantly decreased in TNF-α concentrations in brain homogenates (p <0.01).

Conclusions: ET-1 is significantly increased in TNF-α levels in brain homogenates, while BQ123 given 30 min before administration of ET-1 caused a significant decrease in TNF-α levels, suggesting that its anti-inflammatory activity.

Keywords: ETA receptor blocker (BQ123); TNF-α; brain; endothelin 1.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Brain / drug effects*
  • Brain Chemistry
  • Endothelin Receptor Antagonists / pharmacology*
  • Endothelin-1 / antagonists & inhibitors*
  • Male
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Inbred WKY
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Peptides, Cyclic
  • Tumor Necrosis Factor-alpha
  • cyclo(Trp-Asp-Pro-Val-Leu)