Effects of procaine and two of its metabolites on cisplatin-induced kidney injury in vitro: Mitochondrial aspects.
The protective effects of procaine on cisplatin-induced kidney damage were studied with rat renal cortical slices in vitro. Cisplatin (2 mm) increased the leakage of the enzymes N-acetyl-beta-d-glucosaminidase, aspartate aminotransferase and lactate dehydrogenase from the slices into the incubation medium five-fold, 10-fold and 11-fold, respectively. Procaine (2 mm) protected against this cellular damage and decreased the leakage to 50, 65 and 29% of that caused by cisplatin. Protection was also observed when the slices were treated with two metabolites of procaine [diethylaminoethanol (DEAE) and p-aminobenzoic acid (PABA)], although these were slightly less effective than procaine. Cisplatin also increased mitochondrial lipid peroxidation to 177% of controls, and procaine, DEAE and PABA inhibited this cisplatin-induced increase by 24, 30 and 22%, respectively. Procaine, DEAE and PABA had no effects, however, on either the loss of mitochondrial protein-sulfhydryls or the decrease of Ca(2+) uptake by the mitochondria that were caused by cisplatin. These observations suggest that the protection by procaine and its metabolites results from their inhibitory activity on the mitochondrial lipid peroxidation that was induced by cisplatin.
Zhang
J G
JG
Department of Pharmacology and Therapeutics, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK.
Lindup
W E
WE