Abstract
The marked morphological, functional and biochemical heterogeneity of the kidney accounts for the site-specific toxicity of several drugs and xenobiotics. Puromycin aminonucleoside, daunomycin and adriamycin exert a direct effect on the glomerular epithelial cells, resulting in foot process fusion, accompanied by increased proteinuria, whereas the proximal tubule, in particular the S2 and S3 segments, is the target site for aminoglycoside, cephalosporin, cisplatin, haiogenated alkene and heavy metal toxicity (Commandeur and Vermuelen 1990).This is assumed to be due to the presence of specifc transport processes and/or enzymes e.g. cysteine conjugate C-S lyase, located in the proximal tubule. Ischaemic damage to the proximal tubule is usually confined to the S3 segment or pars recta in the outer medulla, whereas chemically induced proximal tubular injury is dependent on the physicochemical properties of the toxicant and the localisation of transport systems that result in cell-specific accumulation. For example Cd-metallothionein is specifically reabsorbed by the S1 and S2 segments of the proximal tubule, whereas cephaloridine is toxic to the S2 segment, due to the localisation of the organic anion transporter. The cytotoxicity of cysteine S-conjugates is determined by the activities of several enzymes, including cysteine conjugate C-S lyase, localised in the S1 and S3 segments.
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© 1996 Springer-Verlag Berlin Heidelberg
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Hawksworth, G.M., McCarthy, R., McGoldrick, T., Stewart, V., Tisocki, K., Lock, E.A. (1996). Site Specific Drug and Xenobiotic Induced Renal Toxicity. In: Seiler, J.P., Kroftová, O., Eybl, V. (eds) Toxicology - From Cells to Man. Archives of Toxicology, vol 18. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61105-6_19
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DOI: https://doi.org/10.1007/978-3-642-61105-6_19
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