The cardiotoxic effects of acute and chronic grayanotoxin-III in rats

Hum Exp Toxicol. 2020 Mar;39(3):374-383. doi: 10.1177/0960327119889668. Epub 2019 Nov 27.


The purpose of this study is to histologically and immunohistochemically determine the changes created by grayanotoxin-III (GTX-III), which is a sodium channel neurotoxin, on heart tissues in different dosages. Rats were randomly divided into 10 groups to determine the acute and chronic effects of GTX-III. While the rats in groups 1 and 6 were control rats, the rats in groups 2-5 (1, 2, 4, and 8 μg/kg bw GTX-III) received a single dose of intraperitoneal GTX-III, and the rats in groups 7-10 received GTX-III every day for 3 weeks. As a result of the trial, in the heart tissues, histopathological changes were determined by hematoxylin-eosin staining, interleukin-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and brain natriuretic peptide (BNP) were determined by the avidin-biotin peroxidase method, and apoptosis was examined by immunohistochemistry (IHC) analysis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining method. In the immunohistochemistry sense, while the BNP level in the AGTX-III groups did not vary significantly, an increase in dosage significantly increased the IL-6, IL-1β, and TNF-α levels in comparison to the control groups. In their comparison to the control groups, the BNP levels increase and the IL-6 and IL-1β levels decreased in the CGTX-III groups. TUNEL analysis revealed that apoptosis increased in both the acute and chronic groups.

Keywords: Grayanotoxin (GTX)-III; brain natriuretic peptide (BNP); heart; histology; immunohistochemistry (IHC); interleukins.

MeSH terms

  • Animals
  • Diterpenes / administration & dosage
  • Diterpenes / toxicity*
  • Drug Administration Schedule
  • Heart / drug effects*
  • Heart Diseases / chemically induced*
  • Male
  • Myocardium / pathology
  • Rats
  • Rats, Sprague-Dawley


  • Diterpenes
  • grayanotoxin III