Attenuation of DNA damage and mRNA gene expression in hypoxic rats using natural antioxidants

J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21975. Epub 2017 Aug 17.

Abstract

This study aimed to explore the efficiency of carnosine (Cs) and/or l-arginine (Agn) in the downregulation of apoptotic and inflammatory molecule expression and DNA damage caused hepatic injury in response to sodium nitrite (Sd)-induced hypoxia in rats. Rats were injected with Sd; Agn or/and Cs were administrated prior to Sd intoxication. Sd significantly decreased hemoglobin concentration and Bcl-2 mRNA expression, while increased expressions of apoptotic markers (Bax and caspase), tumor necrosis factor-α, nuclear factor kappa B, and C-reactive protein and the oxidative DNA damage in hepatic tissue. Moreover, administration of Agn or/and Cs exhibited a modulation of the previous parameters. However, concurrent treatment with the forementioned antioxidants modulated these levels. It was concluded that the treatment with the combination of Agn and Cs was the most effective regimen in ameliorating Sd toxicity accompanied by hypoxic stress.

Keywords: DNA damage; apoptotic markers; carnosine; hypoxia; inflammatory molecules; l- arginine.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis Regulatory Proteins / metabolism
  • Arginine / pharmacology*
  • C-Reactive Protein / metabolism
  • Carnosine / pharmacology*
  • Caspase 3 / metabolism
  • Cell Hypoxia
  • DNA Damage*
  • Drug Evaluation, Preclinical
  • Gene Expression / drug effects*
  • Hemoglobins / metabolism
  • Male
  • Oxidative Stress / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Hemoglobins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Carnosine
  • C-Reactive Protein
  • Arginine
  • Alanine Transaminase
  • Casp3 protein, rat
  • Caspase 3