Comparison of the toxicities of cisplatin and a new cisplatin-procaine complex to rat renal cortical slices.
1. Procaine has previously been shown to diminish the nephrotoxicity of cisplatin and the nephrotoxic effects of cisplatin and a new cisplatin complex (cis-diamminechloro-[2-(diethylamino) ethyl-4-aminobenzoate, N4]-chlorideplatinum (II) monohydrochloride monohydrate; DPR), that contains procaine hydrochloride were compared with rat renal cortical slices. 2. Cisplatin at 1 mM caused toxicity to the slices, as shown by an increase in the leakage of aspartate aminotransferase and lactate dehydrogenase from the slices into the incubation medium and a decrease in the reduction of a tetrazolium dye (MTT assay). Addition of procaine (1 mM) protected against cisplatin-induced toxicity. DPR either at 1 mM or at 4 mM had no effect either on the enzyme leakage or MTT reduction by the renal slices, but DPR at 10 mM produced a similar magnitude of enzyme leakage to cisplatin (1 mM). 3. DPR lowered the concentration of ATP and glutathione (GSH) in the slices but was less potent than cisplatin. Thiobarbituric acid reactive substances, indicators of lipid peroxidation, released into the medium were increased by the highest concentration of DPR (10 mM), which suggests that DPR has the potential to cause oxidative stress. 4. The results suggest that DPR was far less toxic than either cisplatin alone or a mixture of cisplatin and procaine.
Zhang
J G
JG
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Esposito
M
M
Cafaggi
S
S
Lindup
W E
WE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000633:toxicity*; D011343:Procaine / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013778:Tetrazolium Salts; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances
D000779:Anesthetics, Local; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D017392:Thiobarbituric Acid Reactive Substances; C080075:cisplatin-procaine complex; D011343:Procaine; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; C022616:thiazolyl blue; D005978:Glutathione; D002945:Cisplatin