The influence of ebselen on the toxicity of cisplatin in LLC-PK1 cells.
LLC-PK1 cells have been used as an in vitro model to study the nephrotoxicity of the antitumor drug cisplatin. A concentration-dependent cytotoxicity of cisplatin, measured as lactate dehydrogenase leakage and amount of protein remaining attached to the culture plate, was observed. At a cisplatin concentration of 0.4 mM cell viability was reduced to 21% after 72 hr. Ebselen, a seleno-organic compound capable of forming selenol intermediates through reaction with thiols, was found to protect LLC-PK1 cells against cisplatin-induced toxicity at low concentrations (5-15 microM). The ebselen-induced protection against cisplatin toxicity in this in vitro test system apparently correlates well with a similar protection previously observed in vivo in mice and rats.
Baldew
G S
GS
Interfaculty Reactor Institute Delft University of Technology, The Netherlands.
Boymans
A P
AP
Mol
J G
JG
Vermeulen
N P
NP
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D054833:Isoindoles; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D013552:Swine; D013997:Time Factors
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D007770:L-Lactate Dehydrogenase; D002945:Cisplatin