Ellagic acid confers protection against gentamicin-induced oxidative damage, mitochondrial dysfunction and apoptosis-related nephrotoxicity

J Pharm Pharmacol. 2016 Sep;68(9):1222-32. doi: 10.1111/jphp.12589. Epub 2016 Jun 30.

Abstract

Objectives: The aim of this study was to investigate the possible protective effect of ellagic acid (EA) against gentamicin (GEN)-induced nephrotoxicity using biochemical, molecular and histopathological approaches.

Methods: Rats (n = 24) were divided into four groups: control, GEN (100 mg/kg, i.p.), EA (10 mg/kg, p.o.) and GEN plus EA. The regimes were administered for 10 successive days. 24 h after last treatment, kidney and blood samples were collected.

Key findings: Ellagic acid treatment significantly reduced plasma creatinine and urea levels, which were initially increased due to GEN administration. Also, EA significantly ameliorated oxidative stress markers including lipid peroxidation, catalase (CAT) and superoxide dismutase (SOD) enzyme activity as well as glutathione (GSH) content in kidney tissue. Activation of caspase-3 and increase in the ratio of Bcl-2/Bax expression observed in GEN-treated group were significantly ameliorated by EA treatment. EA also protected GEN-induced mitochondrial damages as indicated by decreasing the mitochondrial ROS content, preventing of mitochondrial membrane potential (MMP) loss, reducing mitochondrial swelling and decreasing cytochrome c release. In addition, histopathological findings revealed that EA ameliorates GEN-induced kidney injury.

Conclusions: Our findings suggest that EA treatment attenuates GEN-induced nephrotoxicity, which may be ascribed to its antioxidant and anti-apoptotic properties.

Keywords: antioxidants; apoptosis; ellagic acid; gentamicin; oxidative stress.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / toxicity
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Apoptosis
  • Caspase 3 / metabolism
  • Creatinine / blood
  • Cytochromes c / metabolism
  • Ellagic Acid / pharmacology
  • Ellagic Acid / therapeutic use*
  • Gentamicins / toxicity*
  • Glutathione / metabolism
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Lipid Peroxidation
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / physiology
  • Oxidative Stress / drug effects*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism
  • Urea / blood

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Gentamicins
  • Plant Extracts
  • Ellagic Acid
  • Urea
  • Cytochromes c
  • Creatinine
  • Superoxide Dismutase
  • Caspase 3
  • Glutathione