Inhibition of lactate-dehydrogenase by cisplatin and other platinum-compounds: enzyme leakage of LDH is not a suitable method to measure platinum-compound-induced kidney cell damage in vitro.
The effects of three platinum-compounds on the activity of hog muscle lactate-dehydrogenase (LDH), cytosolic LDH released from rat renal cortical slices and cytosolic LDH isolated from rat kidney cells were investigated. In vitro, cisplatin inhibited the activity of LDH in a concentration-dependent manner. At a concentration of 0.25 mg/ml, cisplatin, transplatin and cisplatin-hydrolysis-products inhibited the activity of LDH time-dependently. These observations make it doubtful to use LDH-enzyme leakage experiments to demonstrate damage of kidney cells by platinum-compounds. The nonnephrotoxic compound transplatin had an enhanced inhibitory effect on the activity of LDH compared to the nephrotoxic compounds cisplatin or cisplatin-hydrolysis-products (transplatin greater than cisplatin greater than cisplatin-hydrolysis-products). Thus, LDH-enzyme inhibition seems not to be related to the nephrotoxicity of cisplatin.
Hannemann
J
J
Department of Cell Physiology, University of Hamburg, Federal Republic of Germany.
Baumann
K
K
D000818:Animals; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D007536:Isomerism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
C034697:transplatin; D007770:L-Lactate Dehydrogenase; D002945:Cisplatin