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Comparison of the toxicities of cisplatin and a new cisplatin-procaine complex to rat renal cortical slices

Department of Pharmacology and Therapeutics, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK

M. Esposito

Istituto Nazionale per la Ricerca sul Cancro, Servizio di Farmacologia Tossicologica, Viale Benedetto XV, n. 10, 16132 Genova, Italy

S. Cafaggi

Istituto di Analisi e Tecnologie Farmaceutiche, University of Genova, Genova, Italy

WE Lindup

Department of Pharmacology and Therapeutics, University of Liverpool, P.O. Box 147, Liverpool L69 3BX, UK

1 Procaine has previously been shown to diminish the nephrotoxicity of cisplatin and the nephrotoxic effects of cisplatin and a new cisplatin complex (cis-diammine chloro - [2 - (diethylamino) ethyl - 4 - aminobenzoate, N⁴]- chlorideplatinum (II) monohydrochloride monohydrate; DPR), that contains procaine hydrochloride were com pared 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 aminotransfer ase 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.

Key Words: Cisplatin • cisplatin-procaine complex • nephrotoxicity • lipid peroxidation • GSH depletion

Human & Experimental Toxicology, Vol. 15, No. 1, 59-63 (1996)
DOI: 10.1177/096032719601500111


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