Isolated Rat Renal Proximal Tubular Cells: A Model to Investigate Drug Induced Nephrotoxicity
The kidney shows marked functional, morphological and biochemical heterogeneity which may account for the site-specific toxicity of several drugs and xenobiotics. For example, the toxicity associated with cephaloridine and some aminoglycosides is confined to the proximal tubular cells (Kuo and Hook, 1982; Kaloyanides and Pastoriza-Munoz, 1980), whereas prolonged intake of paracetamol results in renal papillary necrosis (Mohandas et al., 1984). To investigate the mechanisms of toxicity using cell suspensions or primary cultures, it is therefore necessary to isolate the different cell types. Several approaches have been used to obtain preparations of proximal tubular cells or fragments. One approach uses existing cell lines of kidney origin (LLC-PK1 or MDCK), the disadvantage being that the exact site of origin within the nephron is not known and, being a cell line, it may not be totally representative of the normal physiological state. A second approach is the digestion or explantation of kidney tissue in the presence of serum-free, hormonally defined culture media such that fibroblast proliferation is minimal and epithelial cell growth is encouraged (Chuman et al., 1982). Unfortunately both these cell preparations lack a brush border, which may be critical for the active uptake of drugs and chemicals.
KeywordsGlutathione Fructose Paracetamol Collagenase Aminoglycosides
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- Endou, H., Koseki, C., Haumara, S., Kakuno, K., Hojo, K., Sakai, F., 1982, Renal cytochrome P450; its localisation along a nephron and its induction, In: “Biochemistry of Kidney Functions”, F. Morel, ed., Elsevier Biomedical PressGoogle Scholar
- Gordon, E.M., McDougall, S.M., Whiting, P.H., Hawksworth, G.M., 1987, Gentamicin-stimulated increase in PAH uptake in renal slices and isolated proximal tubular cells, this volume.Google Scholar
- Gordon, E.M., Whiting, P.H., Simpson, J.G., Hawksworth, G.M., 1987, Isolation and characterisation of rat renal proximal tubular cells, Biochem. Soc. Trans., 15:457Google Scholar
- Goujon, F.M., Nebert, D.W., Gielen, J.E., 1972, Genetic expression of aryl hydrocarbon hydroxylase induction, Mol. Pharm., 8:667Google Scholar
- Vinay, P., Gougoux, A., Lemieux, G., 1981, Isolation of a pure suspension of rat proximal tubules, Am. J. Physiol., 241:403Google Scholar