Bradykinin-potentiating factor isolated from Leiurus quinquestriatus scorpion venom alleviates cardiomyopathy in irradiated rats via remodelling of the RAAS pathway

Clin Exp Pharmacol Physiol. 2020 Feb;47(2):263-273. doi: 10.1111/1440-1681.13202. Epub 2019 Nov 19.

Abstract

The objective of this work was to evaluate the effect of a bradykinin-potentiating factor (BPF) isolated from Leiurus quinquestriatus scorpion venom as a natural modulator of radiation-induced cardiac damage. Four groups of rats were treated as follows; control group, group receiving BPF (1 µg/g b.wt i.p./biweekly) for 4 weeks, group irradiated at 6 Gy, group receiving BPF post-irradiation for 4 weeks. Irradiation induced a significant elevation of myocardial parameters: atrial natriuretic peptide (ANP), cardiac troponin I (cTnI), potassium (K+ ) and creatine kinase (CK); vascular indices: lactate dehydrogenase (LDH), inducible nitric oxide synthase (iNOS) and endothelin I; oxidative stress indices: malondialdehyde (MDA) associated with a significant depletion of both reduced glutathione (GSH) in the cardiac tissue homogenate and serum ferric reducing antioxidant power (FRAP) depletion and significantly reinforced elevation of Renin Angiotensin Aldosterone System (RAAS) indices: serum angiotensin II (AngII) and aldosterone, and also protein expression of cleaved caspase-3 and cyclophilin A. BPF administration altered the biochemical damage of radiation, specifically inhibited AngII formation, aldosterone release and prevented the histopathological and immunohistochemical alterations which were observed in cardiac tissue with significant reduction in mean arterial blood pressure (MAP) caused by irradiation. In conclusion, biochemical assays, histopathological and immunohistochemical findings of the present study demonstrated that exogenous BPF isolated from scorpion venom reduced the cardiomyopathy alterations induced by irradiation via remodelling of the RAAS pathway.

Keywords: Leiurus quinquestriatus; BPF; RAAS; cardiomyopathy; irradiation.

MeSH terms

  • Animals
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Gamma Rays / adverse effects*
  • Male
  • Oligopeptides / isolation & purification
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use*
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology
  • Renin-Angiotensin System / radiation effects
  • Scorpion Venoms / isolation & purification
  • Scorpion Venoms / pharmacology
  • Scorpion Venoms / therapeutic use*

Substances

  • Oligopeptides
  • Scorpion Venoms
  • bradykinin potentiating factors