Possible use of excretion of tubular epithelial cells for the study of the nephrotoxic effect of xenobiotics.
The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1 mg/kg, i.v.), which produced up to 12-fold increases in the number of excreted epithelial cells, was examined. Repeated administration of cyclosporin A (45 and 56 mg/kg, p.o.) produced up to 23-fold increases in the number of excreted epithelial cells. The degree of excretion of epithelial cells after administration of both drugs was compared with the urinary excretion of alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, which indicated nephrotoxicity in amphotericin B and cyclosporin A with a lower sensitivity than the increase in the excretion of epithelial cells. In the experiment with cyclosporin A, urinary excretion of epithelial cells was further correlated with renal functional tests (clearance of polyfructosan and hippurate.
Stĕtinová
V
V
Institute of Experimental Biopharmaceutics, Joint Laboratories of the Academy of Sciences of the Czech Republic, Hradec Králové, Czech Republic.
Trejtnar
F
F
Kopecký
J
J
Grossmann
V
V
Kvètina
J
J
Kopecká
L
L
Semecký
V
V
D000118:Acetylglucosaminidase / Q000652:urine; D000666:Amphotericin B / Q000633:toxicity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D018826:CD13 Antigens / Q000652:urine; D016572:Cyclosporine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006626:Hippurates / Q000652:urine; D007166:Immunosuppressive Agents / Q000633:toxicity; D007457:Iodine Radioisotopes; D007674:Kidney Diseases / Q000139:chemically induced*; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014116:Toxicology / Q000379:methods; D014556:Urine / Q000166:cytology*; D015262:Xenobiotics / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D006626:Hippurates; D007166:Immunosuppressive Agents; D007457:Iodine Radioisotopes; D015262:Xenobiotics; D000666:Amphotericin B; D016572:Cyclosporine; D000118:Acetylglucosaminidase; D018826:CD13 Antigens; C030514:hippuric acid