Ellagic Acid Confers Protection Against Gentamicin-Induced Oxidative Damage, Mitochondrial Dysfunction and Apoptosis-Related Nephrotoxicity Publisher Pubmed



Sepand MR¹ ; Ghahremani MH¹ ; Razaviazarkhiavi K² ; Aghsami M¹ ; Rajabi J³ ; Keshavarzbahaghighat H¹ ; Soodi M⁴
Source: Journal of Pharmacy and Pharmacology Published:2016

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. © 2016 Royal Pharmaceutical Society