New platinum complex compounds with reduced nephrotoxicity discovered in long-term histoculture of human renal cortical tissue.
Cisplatinum is often effective in cancer treatment, but potent nephrotoxicity limits its clinical use. We have synthesized six new platinum compounds with the goal of reducing toxicity while maintaining efficacy. We initially tested drugs at 5 x 10(-4)M with 48 hours exposure in monolayer cultures of primary rabbit proximal tubular cells and human renal cortical cells with the MTT endpoint to measure toxicity. Drug concentration of 10(-3)M, 10(-4)M and 10(-5)M with 72 hours exposure were used for human renal cortical tissues in 7 week sponge-gel-supported histoculture with toxicity measured by the glucose-consumption endpoint. From these studies, we determined that the new platinum drugs have lower nephrotoxicity than cisplatinum.
Chang
S G
SG
Department of Urology, Kyung Hee University, Seoul, Korea.
Kwon
D U
DU
Kim
J I
JI
Jung
J C
JC
Rho
Y S
YS
Hoffman
R M
RM
D000970:Antineoplastic Agents / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D009944:Organoplatinum Compounds / Q000633:toxicity*; D017671:Platinum Compounds / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D005947:Glucose