Cisplatin-induced toxicity in LLC-PK1 kidney epithelial cells: role of basolateral membrane transport.
Cytotoxicity of cisplatin was evaluated after apical and/or basolateral treatment of LLC-PK1 cell monolayers grown on porous membrane filters with 300 microM cisplatin. When LLC-PK1 cells were exposed from basolateral side for 0.5-4 h, lactate dehydrogenase (LDH) release into culture medium was markedly stimulated. However, apical treatment of the cells with cisplatin for 0.5 h did not stimulate LDH release. gamma-Glutamyltransferase activity and amount of protein in the cell homogenate were markedly decreased by basolateral treatment with cisplatin. However, in the apical treatment with cisplatin, these changes were relatively small, suggesting that degrees of the toxicities were different between basolateral and apical treatment with cisplatin. Cellular platinum level after basolateral treatment with cisplatin was higher compared to that following apical treatment. Furthermore, both accumulation and toxicity of cisplatin in LLC-PK1 cells were decreased by treatment with cisplatin at 4 degrees C. These results suggested that there were specific mechanisms mediating cisplatin uptake at the basolateral membranes of LLC-PK1 cells.
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
M
M
Okuda
K
K
Tsuda
K
K
Masaki
Y
Y
Hashimoto
K
K
Inui
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001692:Biological Transport; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018374:LLC-PK1 Cells; D013552:Swine; D013696:Temperature; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000970:Antineoplastic Agents; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D002945:Cisplatin