Protective effects of a glutathione disulfide mimetic (NOV-002) against cisplatin induced kidney toxicity - 04/01/10
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Abstract |
NOV-002 is a glutathione disulfide (GSSG) mimetic with chemoprotective activity. Previous and ongoing clinical studies demonstrate a significantly improved 1-year survival and decreased tumor progression rates in non-small cell lung (NSCLC) and ovarian cancer patients when NOV-002 was included in cisplatin containing regimens. In order to understand this chemoprotective property, we employed as an animal model of kidney toxicity, 8-week-old Bl6 mice that were treated with a single nephrotoxic dose of cisplatin (15mg/kg, ip) and sacrificed on Day 5. One group of animals was treated with NOV-002 (15mg/kg, im) daily. NOV-002-treated mice had significantly lower levels of plasma creatinine compared to mice treated with cisplatin alone (4.7 vs 2.9mg/dL, respectively). Moreover, NOV-002 protected the kidneys from cisplatin mediated proximal tubule damage, including dilation of tubules and the presence of protein casts. Since cisplatin-induced nephrotoxicity can be mediated by a glutathione-platinum conjugate catalyzed by γ-glutamyl-transpeptidase (GGT) and glutathione is an endogenous substrate of GGT, the protective effect of NOV-002 in the kidney may be attributed to its ability to act as a competitive substrate for the enzyme.
Le texte complet de cet article est disponible en PDF.Abbreviations : GSH, GSSG, GGT
Keywords : Glutathione, Cisplatin, Nephrotoxicity, NOV-002, Chemoprotection
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Vol 64 - N° 1
P. 73-76 - janvier 2010 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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