Investigative study of drug-induced nephropathy using renal cortical slice technique and cultured cell line

为探讨甲基强的松龙预防顺铂肾毒性的作用机制，进行了甲基强的松龙对顺铂肾毒性保护作用的临床研究。甲基强的松龙导致尿铂排泄增加，同时伴有肾铂浓度下降。为探讨甲基强的松龙对抗顺铂肾毒性的临床应用价值，将大鼠和人肾皮质组织切片，分别与头孢吡啶(CER)或庆大霉素(GM)孵育，观察肾皮质切片技术的有效性。大鼠肾切片中NAG的释放呈剂量依赖性。与CER孵育的大鼠肾切片未见剂量相关的γ-GTP释放。与大鼠肾组织相比，CER孵育的人肾组织释放的NAG较少。人肾组织对CER肾毒性较不敏感。通用汽车没有与…签约对大鼠或人肾切片的酶释放影响更大。通过对顺铂肾毒性的评价，探讨了肾皮质切片技术作为药物肾毒性体外检测系统的有效性。NAG、γ-GTP和LDH呈剂量依赖性增加。顺铂可显著减少多环芳烃在肾切片中的蓄积。观察顺铂对肾切片糖异生的抑制作用。提示肾皮质切片技术可定量检测顺铂对肾上皮细胞的毒性作用。肾皮质薄片技术是评价顺铂肾毒性的一种简便、经济的体外检测系统。为评价造影剂肾病，采用非离子LOOM技术对低渗透造影剂(LOOM)的肾毒性进行了检测。采用大鼠肾皮质切片技术比较了LOOM与离子型高渗造影剂(HOOM)的肾毒性作用。尿NAG、γ-GTP是诊断造影剂肾病的敏感指标。临床研究表明，非离子织机对肾小管细胞有损伤作用，而血清肌酐或肌酐清除率检测不出肾小管细胞损伤。肾皮质切片技术显示，非离子织机的肾毒性与离子型HOCM相当。较少

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 … More 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