[Drug-induced nephrotoxicity].
The incidence of drug-induced nephrotoxicity (DIN) has recently been increasing. Based on developments in molecular biology and cell biology, cultured cells have become a very useful tool for investigating DIN. Especially, the immortalized cell lines derived from well-defined nephron segments are ideal for such studies. As indicators to detect DIN, myosin light chain phosphorylation in glomerular mesangial cells, enzymes of proximal tubule origin such as glycine-amidinotransferase, cytosolic free calcium concentration and intracellular ATP content may be useful. The involvement of nitric oxide and heat shock protein in DIN has been reported. Therapeutic effects of growth factors such as HGF or EGF for DIN have been identified. The direct evidence for the involvement of reactive oxygen species and the molecular basis for redox regulation in DIN is required. Cisplatin has been shown to induce apoptosis, and the role of apoptosis in DIN remains to be further clarified. Thus, in parallel with in vivo studies, cultured cells provide an opportunity for clarifying the intracellular mechanism for DIN more precisely and establishing an efficient screening system to develop drugs to prevent DIN.
Takeda
M
M
Department of Pharmacological and Toxicology, Kyorin University School of Med
Endou
H
H
D000579:Amidinotransferases / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002945:Cisplatin / Q000009:adverse effects; D005839:Gentamicins / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005839:Gentamicins; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D000579:Amidinotransferases; C020681:glycine amidinotransferase; D002945:Cisplatin; D002118:Calcium