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

通过实验研究甲基强的松龙对顺铂肾毒性的预防作用机制，临床研究证实甲基强的松龙对顺铂肾毒性的保护作用。甲基强的松龙诱导尿铂排泄增加，同时伴有肾铂浓度降低。指出甲基强的松龙抗顺铂肾毒性的临床应用价值。用头孢洛啶（CER）或庆大霉素（GM）孵育大鼠和人肾皮质组织，以检验肾皮质切片技术的有效性。NAG在大鼠肾片中的释放与CER浓度呈剂量依赖性。经CER孵育的大鼠肾片γ - gtp未见剂量相关释放。与大鼠肾组织相比，CER培养的人肾组织中NAG的释放量较少。人肾组织对CER肾毒性较不敏感。转基因对大鼠和人肾片酶释放均无显著影响。该体外系统是一种简单、经济的药物肾毒性评价系统。通过评价顺铂的肾毒性，探讨肾皮质切片技术作为一种体外检测药物性肾毒性的方法的有效性。NAG、γ - gtp、LDH均呈剂量依赖性升高。顺铂可显著降低肾片中多环芳烃的积累。观察顺铂对肾切片糖异生的抑制作用。这些结果表明，通过肾皮质切片技术可以定量地测定顺铂对肾上皮细胞的毒性作用。肾皮质片技术是一种简单、经济的体外评价顺铂肾毒性的方法。为了评估造影剂肾病，在接受非离子型造影剂造影检查的患者中检查了低渗透性造影剂（LOOM）的肾毒性。采用肾皮质切片技术，在大鼠肾组织中比较了离子高渗透压造影剂（LOOM）和离子高渗透压造影剂（HOOM）的肾毒性。尿NAG和γ - gtp是造影剂肾病的敏感指标。临床研究表明，非离子型LOOM损伤肾小管细胞，而血清肌酐或肌酐清除率不能检测到这些肾损伤。肾皮质片技术显示非离子型LOOM与离子型HOCM具有同样的肾毒性。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