title: Ellagic acid confers protection against gentamicin-induced oxidative damage, mitochondrial dysfunction and apoptosis-related nephrotoxicity.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Sepand
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Kamal
authors.initials: K
authors.lastname: Razavi-Azarkhiavi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Aghsami
authors.affiliation: Department of Internal Medicine, School of Medical Sciences, AJA University of Medical Sciences, Tehran, Iran.
authors.forename: Jalil
authors.initials: J
authors.lastname: Rajabi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hedieh
authors.initials: H
authors.lastname: Keshavarz-Bahaghighat
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Soodi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D045304:Cytochromes c / Q000378:metabolism; D004610:Ellagic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005839:Gentamicins / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005839:Gentamicins; D010936:Plant Extracts; D004610:Ellagic Acid; D014508:Urea; D045304:Cytochromes c; D003404:Creatinine; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione
keywords: antioxidants; apoptosis; ellagic acid; gentamicin; oxidative stress