title: Protective effect of CV247 against cisplatin nephrotoxicity in rats.
abstract: CV247 (CV), an aqueous mixture of copper (Cu) and manganese (Mn) gluconates, vitamin C and sodium salicylate increased the antitumour effects of cisplatin (CDPP; cis-diamminedichloroplatinum) in vitro. We hypothesized that the antioxidant and cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2) inhibitory components of CV can protect the kidneys from CDPP nephrotoxicity in rats. CDPP (6.5 mg/kg, intraperitoneally) slightly elevated serum creatinine (Crea) and blood urea nitrogen (BUN) 12 days after treatment. Kidney histology demonstrated extensive tubular epithelial damage and COX-2 immunoreactivity increased 14 days after treatment. A large amount of platinum (Pt) accumulated in the kidney of CDPP-treated rats. Furthermore, CDPP decreased renal iron (Fe), molybdenum (Mo), zinc (Zn), Cu and Mn concentrations and increased plasma Fe and Cu concentrations. CDPP elevated plasma free radical concentration. Treatment with CV alone for 14 days (twice 3 ml/kg/day orally) did not influence these parameters. Chronic CV administration after CDPP reduced renal histological damage and slightly decreased COX-2 immunoreactivity, while failed to prevent the increase in Crea and BUN levels. Blood free radical concentration was reduced, that is, CV improved redox homeostasis. CV restored plasma Fe and renal Fe, Mo and Zn, while decreased Pt and elevated Cu and Mn concentrations in the kidney. Besides the known synergistic antitumour effects with CDPP, CV partially protected the kidneys from CDPP nephrotoxicity probably through its antioxidant effect.
authors: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors: C
authors: C
authors: Máthé
authors: Institute of Pathophysiology, Semmelweis University, Budapest, Hungary szenasi.gabor@med.semmelweis-univ.hu.
authors: G
authors: G
authors: Szénási
authors: Laboratory Animal Science Unit, Faculty of Veterinary Science, Szent István University, Budapest, Hungary.
authors: A
authors: A
authors: Sebestény
authors: Department of Pharmacognosy, Semmelweis University, Budapest, Hungary.
authors: A
authors: A
authors: Blázovics
authors: Institute of Materials and Environmental Chemistry Research Centre for Natural Sciences, Budapest, Hungary.
authors: K
authors: K
authors: Szentmihályi
authors: Institute of Pathophysiology, Semmelweis University, Budapest, Hungary.
authors: P
authors: P
authors: Hamar
authors: Vetmed Laboratory Ltd, Budapest, Hungary.
authors: M
authors: M
authors: Albert
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D005942:Gluconates / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008670:Metals / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000097:blood; D012980:Sodium Salicylate / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D005942:Gluconates; D008670:Metals; D017382:Reactive Oxygen Species; D003404:Creatinine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D001205:Ascorbic Acid; D002945:Cisplatin; D012980:Sodium Salicylate
keywords: antioxidant; cisplatin; cyclooxygenase-2; nephrotoxicity; salicylate