Thymol attenuates inflammation in isoproterenol induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines

Eur J Pharmacol. 2015 May 5:754:153-61. doi: 10.1016/j.ejphar.2015.02.028. Epub 2015 Feb 25.

Abstract

Inflammation plays an important role in the development of myocardial infarction (MI). The current study dealt with the protective effects of thymol on inflammation in isoproterenol (ISO) induced myocardial infarcted rats. Male albino Wistar rats were pre and co-treated with thymol (7.5mg/kg body weight) daily for 7 days. ISO (100mg/kg body weight) was injected subcutaneously into rats at an interval of 24h for two days (6th and 7th day) to induce MI. ISO induced myocardial infarcted rats showed increased levels of serum cardiac troponin-T, high sensitive C-reactive protein (hsCRP), lysosomal thiobarbituric acid reactive substances (TBARS) and elevated ST-segments. Also, the activities of lysosomal enzymes such as β-glucuronidase, β-galactosidase, cathepsin-B and D, the stimulators of inflammatory mediators were increased in the serum and heart of ISO induced myocardial infarcted rats. Furthermore, ISO up regulates the expressions of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) genes in the myocardium of rats analyzed by reverse transcription polymerase chain reaction (RT-PCR). Pre and co-treatment with thymol (7.5mg/kg body weight) near normalized the levels of lysosomal TBARS, activities of serum and heart lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines in the myocardium of ISO induced myocardial infarcted rats. Histopathological and transmission electron microscopic findings were also found in line with biochemical findings. Thus, the results of our study revealed that thymol attenuates inflammation by inhibiting the release of lysosomal enzymes and downregulates the expressions of pro-inflammatory cytokines by its potent anti-inflammatory effect.

Keywords: Inflammation; Isoproterenol; Lysosomal enzymes; Myocardial infarction; Pro-inflammatory cytokines; Thymol.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • C-Reactive Protein / metabolism
  • Cytokines / metabolism*
  • Down-Regulation / drug effects*
  • Electrocardiography
  • Heart / drug effects
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Isoproterenol
  • Lipid Peroxidation / drug effects
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Lysosomes / ultrastructure
  • Male
  • Myocardial Infarction / blood
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / enzymology*
  • Myocardial Infarction / pathology*
  • Myocardium / enzymology
  • Myocardium / immunology
  • Myocardium / pathology
  • Myocardium / ultrastructure
  • Rats
  • Thiobarbituric Acid Reactive Substances
  • Thymol / pharmacology*
  • Thymol / therapeutic use*
  • Troponin T / blood
  • Up-Regulation / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Thiobarbituric Acid Reactive Substances
  • Troponin T
  • Thymol
  • C-Reactive Protein
  • Isoproterenol