Comparative nephrotoxicity of some antitumour-active platinum and ruthenium complexes in rats.
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 LD450 of the compounds given twice a week for up to 5 weeks. After a relatively high single dose of the substances (50% of the LD50), 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.
Kersten
L
L
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany. hzub@mti-n.uni-jena.de
Bräunlich
H
H
Keppler
B K
BK
Gliesing
C
C
Wendelin
M
M
Westphal
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity; D005260:Female; D007668:Kidney / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D017671:Platinum Compounds / Q000633:toxicity*; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000633:toxicity*
D000970:Antineoplastic Agents; D017671:Platinum Compounds; D017975:Ruthenium Compounds; D002945:Cisplatin