Concerted hepatoprotective effect of bradykinin potentiating factor and low dose of γ- radiation on Naja haje envenomed rats via Bax/Bcl2 pathway

Toxicol Mech Methods. 2022 Jan;32(1):67-76. doi: 10.1080/15376516.2021.1965276. Epub 2021 Aug 22.

Abstract

This study investigates the concerted hepatoprotective effects for three doses of bradykinin potentiating factor (BPF) and/or followed by exposure to a low dose of γ-radiation (LDR) against Naja haje envenoming in rats. Male rats were injected with three consecutive doses of BPF (1 μg/g i.p. for 3 days), followed by exposure to a low dose of gamma radiation (0.5 Gy), and then rats were injected with a dose of Naja haje venom (250 μg/kg i.p.). Results showed that Naja haje causes liver damage, significant elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cytochrome c, Nitric oxide (NO), malondialdehyde (MDA) and significant depletion in glutathione peroxidase (GPx) contents. In addition, significant depletion in B-cell lymphoma 2 (Bcl-2) and significant elevation in BcL-2 associated X (Bax protein), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β) in hepatocytes. Bradykinin potentiating factor and/or low dose of γ-radiation caused improvement in liver damage caused by Naja haje venom by a significant decrease in ALT, AST, ALP levels, Bax, cytochrome c, NF-κB, IL-1β, NO and MDA contents, BPF alone or combined with low dose radiation caused a significant increase in Bcl2 and GPx contents. In conclusion, the concerted impact of BPF and LDR may provide an effective venom detoxification tool that helps to reduce hepatic toxicity and extends the lifespan.

Keywords: Bax; Bcl2; Bradykinin potentiating factor; Naja haje; γ-radiation.

MeSH terms

  • Animals
  • Bradykinin* / metabolism
  • Gamma Rays
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Naja haje*
  • Oxidative Stress
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Snake Bites* / drug therapy
  • Snake Bites* / radiotherapy
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Bcl2 protein, rat
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Bradykinin