Protective effect of CV247 against cisplatin nephrotoxicity in rats

C. Máthé, G. Szénási, A. Sebestény, A. Blázovics, K. Szentmihályi, P. Hamar, M. Albert

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)789-799
Number of pages11
JournalHuman and Experimental Toxicology
Volume33
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Cisplatin
Rats
Blood
Molybdenum
Manganese
Platinum
Kidney
Plasmas
Free Radicals
Urea
Zinc
Creatinine
Nitrogen
Antioxidants
Sodium Salicylate
Histology
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Ascorbic Acid
Copper

Keywords

  • antioxidant
  • cisplatin
  • cyclooxygenase-2
  • nephrotoxicity
  • salicylate

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Protective effect of CV247 against cisplatin nephrotoxicity in rats. / Máthé, C.; Szénási, G.; Sebestény, A.; Blázovics, A.; Szentmihályi, K.; Hamar, P.; Albert, M.

In: Human and Experimental Toxicology, Vol. 33, No. 8, 2014, p. 789-799.

Research output: Contribution to journalArticle

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