1998 Fiscal Year Final Research Report Summary
Investigative study of drug-induced nephropathy using renal cortical slice technique and cultured cell line
| Project/Area Number |
08671822
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
UOZUMI Jiro Kyushu University, Faculty of Medicine, Department of Urology, Assistant Professor, 医学部, 講師 (30223514)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUDA Noriaki Kyushu University, Faculty of Medicine, Department of Urology, Assistant Profess, 医学部, 助手 (20264038)
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| Project Period (FY) |
1996 – 1998
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| Keywords | antibiotics / cisplatin / contrast medium / methylprednisolone / drug-induced nephropathy / NAG / gamma-GTP / renal cortical slice |
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| Research Abstract |
Experimental study to investigate the mechanism of prophylactic effect of methylprednisolone on cisplatin nephrotoxicity and clinical study to confirm the protective effects of methylprednisolone against cisplatin nephrotoxicity were conducted. Methylprednisolone induced increase in urinary platinum excretion, accompanied by a decrease in kidney platinum concentrations. The clinical usefulness of methylprednisolone against cisplatin nephrotoxicity were indicated.
Renal cortical tissue prepared from rat and human were sliced and incubated with cefaloridine (CER) or gentamicin (GM) to examine the usefulness of renal cortical slice techniques. NAG was released from rat renal slice dose-dependently on CER concentration. Dose-related release of gamma-GTP from rat renal slice incubated with CER was not found. NAG release from human kidney tissue incubated with CER were less compared with that from rat kidney tissue. Human kidney tissue was less sensitive to CER nephrotoxicity. GM did not sign
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ificantly affect the enzyme release either from rat or human renal slice. This in vitro system is a simple and economical assay system to evaluate the drug-induced nephrotoxicity.
The usefulness of renal cortical slice technique as an in vitro assay system to detect drug-induced nephrotoxicity was studied by evaluating the renal toxicity of cisplatin. Dose dependent increases of NAG, gamma-GTP, and LDH were observed. PAH accumulation in kidney slices was significantly reduced by cisplatin. Inhibitory effect of cisplatin on gluconeogenesis in renal slices was observed. These results suggested that toxic effect of cisplatin on renal epithelial cells was quantitatively determined by renal cortical slice technique. Renal cortical slice technique is a simple and economical in vitro assay system for evaluating cisplatin nephrotoxicity.
To evaluate the contrast medium nephropathy, nephrotoxicity of low-osmolality contrast medium (LOOM) were examined in patients received radiographic studies using nonionic LOOM.Nephrotoxic effects of LOOM were compared with those of ionic high-osmolality contrast medium (HOOM) by renal cortical slice technique using rat renal tissue. Urinary NAG and gamma-GTP were sensitive indicators for contrast medium nephropathy. The clinical investigation suggested that nonionic LOOM injured renal tubular cells, while those renal damage can not be detected by serum creatinine or creatinine clearance. Renal cortical slice technique revealed that nonionic LOOM was as nephrotoxic as ionic HOCM. Less
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