The effect of acute ophiobolin A treatment on HO-mediated inflammatory processes

Hum Exp Toxicol. 2017 Jun;36(6):594-602. doi: 10.1177/0960327116658107. Epub 2016 Jul 10.

Abstract

Many microbial and plant-derived metabolites contribute to the production of inflammatory mediators and the expression of pro-inflammatory molecules. Ophiobolin A (OPA) is a fungal secondary metabolite produced by Bipolaris species. The aim of our study was to examine the acute effects of this compound on inflammatory processes. Male Wistar rats were treated with 5% ethanol, 0.01 mg/kg OPA, 0.1 mg/kg OPA and 1.0 mg/kg OPA per os. After 24 h of the administrations, inflammatory mediators such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) enzyme as well as heme oxygenase (HO) activity were measured in both plasma and cardiac tissue, along with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We found that OPA caused a significant elevation in the concentrations of IL-6 and TNF-α, increased MPO activity and decreased HO enzyme activity in the plasma. While OPA induces inflammation in the plasma, it did not change the level of inflammatory mediators in the cardiac tissue and the concentrations of serum ALT and AST. Our findings indicate that rapid release of inflammatory mediators by OPA promotes systemic inflammation. However, this acute OPA treatment does not show toxic effects on the cardiac tissue and the concentrations of liver enzymes.

Keywords: Ophiobolin A (OPA); heme oxygenase; inflammation; myeloperoxidase; pro-inflammatory cytokines.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Heme Oxygenase (Decyclizing) / blood
  • Heme Oxygenase (Decyclizing) / metabolism
  • Inflammation / blood
  • Inflammation / chemically induced
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Male
  • Peroxidase / blood
  • Peroxidase / metabolism
  • Rats, Wistar
  • Sesterterpenes / toxicity*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Sesterterpenes
  • Tumor Necrosis Factor-alpha
  • ophiobolin A
  • Peroxidase
  • Heme Oxygenase (Decyclizing)
  • Aspartate Aminotransferases
  • Alanine Transaminase