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Comparative nephrotoxicity of some antitumour‐active platinum and ruthenium complexes in rats
Author(s) -
Kersten Lothar,
Bräunlich Helmut,
Keppler Bernhard K.,
Gliesing Christiane,
Wendelin Matthias,
Westphal Jens
Publication year - 1998
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/(sici)1099-1263(199803/04)18:2<93::aid-jat472>3.0.co;2-w
Subject(s) - ruthenium , nephrotoxicity , platinum , chemistry , pharmacology , toxicology , toxicity , combinatorial chemistry , medicine , biochemistry , biology , organic chemistry , catalysis
The nephrotoxicity of three platinum (CPL, KP734, KP735) and three ruthenium coordination complexes (KP418, KP692, KP1019) was tested in rats in comparison to cisplatin (CP). Renal functional changes (excretion of water, protein, p ‐aminohippurate (PAH) and osmolytes) were not observed after the administration of 10% of the LD 50 of the compounds given twice a week for up to 5 weeks. After a relatively high single dose of the substances (50% of the LD 50 ), signs of nephrotoxicity on the day of maximal renal damage decreased in the following order: CP, KP418, CPL, KP734, KP735, KP692 and KP1019. In comparison to CP, proteinuria was significantly lower after the administration of any of the compounds, especially KP692 and KP1019. Neither renal lipid peroxidation (TBARS) nor glutathion status (GSH, GSSG) was affected. In summary, KP735 in the group of platinum complexes and KP1019 in the ruthenium group had the lowest nephrotoxicity. Other investigators have shown that all complexes induced anti‐neoplastic activity under analogous experimental conditions. © 1998 John Wiley & Sons, Ltd.