Resveratrol Pretreatment Ameliorates p53-Bax Axis and Augments the Survival Biomarker B-Cell Lymphoma 2 Modulated by Paracetamol Overdose in a Rat Model of Acute Liver Injury

Pharmacology. 2020;105(1-2):39-46. doi: 10.1159/000502632. Epub 2019 Sep 25.

Abstract

Background: The potential protective effects of resveratrol (RES) on the modulation of hepatic biomarkers of apoptosis and survival, p53-Bax axis, and B-cell lymphoma 2 (Bcl-2) in an animal model of paracetamol-induced acute liver injury have not been investigated before.

Methods: The model group of rats received a single dose of paracetamol (2 g/kg, orally), whereas the protective group of rats were pretreated for 7 days with RES (30 mg/kg, i.p.) before they were given a single dose of paracetamol. All rats were then sacrificed 24-h post paracetamol ingestion.

Results: Histology images showed that paracetamol overdose induced acute liver injury, which was substantially protected by RES. Paracetamol significantly (p < 0.05) modulated p53, apoptosis regulator Bax, Bcl-2, tumor necrosis factor-alpha, interleukin-6, inducible nitric oxide synthase, malondialdehyde, superoxide dismutase, glutathione peroxidase, alanine aminotransferase, and aspartate aminotransferase, which were significantly protected by RES. We further demonstrated a significant (p< 0.01) correlation between either p53 or Bcl-2 scoring and the levels of inflammatory, nitrosative stress, and liver injury biomarkers.

Conclusion: We demonstrate a substantial protection by RES pretreatment against paracetamol-induced modulation of p53-Bax axis, Bcl-2, and other acute liver injury biomarkers in rats.

Keywords: Acute liver injury; B-cell lymphoma 2; Paracetamol; Rat model; Resveratrol; p53-Bax axis.

MeSH terms

  • Acetaminophen / toxicity*
  • Alanine Transaminase / metabolism
  • Analgesics, Non-Narcotic / toxicity*
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Aspartate Aminotransferases / metabolism
  • Biomarkers / metabolism
  • Chemical and Drug Induced Liver Injury* / genetics
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / pathology
  • Disease Models, Animal
  • Drug Overdose
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats, Wistar
  • Resveratrol / pharmacology*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Analgesics, Non-Narcotic
  • Antioxidants
  • Biomarkers
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Acetaminophen
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Resveratrol