Toxicity of cisplatin and mercuric chloride in human kidney cortical slices.
1. Organ specific toxicity such as nephrotoxicity is often investigated with the use of in vivo or in vitro animal models. 2. It would be beneficial if these findings could be verified in a human in vitro system which utilizes non-transplantable human kidneys. 3. Non-transplantable human kidneys were decapsulated, cut in half along the long axis, cores made perpendicular to the hemisphere, and precision-cut renal cortical slices produced. 4. These human kidney slices were incubated for 3, 6, 12, 18 and 24 h, viability assessed using intracellular K+ content, protein synthesis and organic ion transport and the potential nephrotoxicity of cisplatin (0.25, 0.5 and 1.0 mM) and mercuric chloride (10, 50 and 100 microM) on these slices were examined. 5. Control human kidney slices were viable for up to 24 h using all viability parameters while a dose- and time-dependent toxic response was seen using both cisplatin and mercuric chloride. 6. Cisplatin was more nephrotoxic in this human in vitro system than in previously investigated in vitro animal systems whereas mercuric chloride was similar in both systems. 7. These results indicate that human renal cortical slices are useful in predicting and verifying potentially nephrotoxic compounds in man.
Fisher
R L
RL
Department of Pharmacology, University of Arizona, Tucson 85724.
Sanuik
J T
JT
Gandolfi
A J
AJ
Brendel
K
K
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D002945:Cisplatin / Q000633:toxicity*; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D017136:Ion Transport; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008875:Middle Aged; D011188:Potassium / Q000378:metabolism; D014176:Protein Biosynthesis; D014021:Tissue Preservation
D008627:Mercuric Chloride; D002945:Cisplatin; D011188:Potassium