title: Ellagic acid protects against cisplatin-induced nephrotoxicity in rats: a dose-dependent study.
abstract: BACKGROUND
  The anticancerdrug cisplatin (CP) causes nephrotoxicity through different mechanisms, including generation of free radicals. Ellagic acid (EA) is a polyphenolic antioxidant found in fruits and nuts.
  
  
  OBJECTIVE
  This study aimed to investigate the ability of different doses of EA to ameliorate CP nephrotoxicity in rats.
  
  
  METHODS
  Animals were randomly divided into six groups and treated with saline; CP alone (6 mg/kg); two doses of EA, both alone (10 and 30 mg/kg) or with CP.
  
  
  RESULTS
  Treatment with CP alone reduced body weight, water intake, urine output, and renal total antioxidant and reduced glutathione (GSH) concentrations (p < 0.01). In addition, it increased relative kidney weight, plasma creatinine, and blood urea nitrogen (BUN) concentrations (p < 0.01). However, a dose of 30 mg/kg EA mitigated most of the CP-induced actions, but no effect was seen for the 10 mg/kg dose. Histopathologically, rats given CP+EA30 showed < 25% necrotic lesions in the renal cortical area compared with > 60% in rats treated with CP alone. Molecular analysis showed that clusterin (Clu) mRNA and protein were expressed in all treated groups, meanwhile kidney injury molecule-1 (Kim-1) mRNA and protein were only expressed in the CP and CP+EA treated rats.
  
  
  CONCLUSIONS
  EA (30 mg/kg) ameliorated most of the physiological, histological, and biochemical markers of CP nephrotoxicity. The molecular findings in this work did not completely tally with the conventional method used. The overexpression of the molecular markers may be related to the EA induced repair mechanism.
authors: Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod, Oman.
authors: N
authors: N
authors: Al-Kharusi
authors: H A
authors: HA
authors: Babiker
authors: S
authors: S
authors: Al-Salam
authors: M I
authors: MI
authors: Waly
authors: A
authors: A
authors: Nemmar
authors: I
authors: I
authors: Al-Lawati
authors: J
authors: J
authors: Yasin
authors: S
authors: S
authors: Beegam
authors: B H
authors: BH
authors: Ali
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D002945:Cisplatin / Q000633:toxicity*; D051152:Clusterin / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D002945:Cisplatin; D051152:Clusterin; D004610:Ellagic Acid; D012333:RNA, Messenger; C110936:Havcr1 protein, rat