Namikawa K, Hirai K, Kitano T, Tanaka I, Miyauchi K, Minami T, Okazaki Y, Kadota E
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Yakugaku Zasshi. 1999 Dec;119(12):936-44. doi: 10.1248/yakushi1947.119.12_936.
The effects of allopurinol (Allop) on the lipid peroxidation in the nephrotoxicity of an antitumor drug, cisplatin (CDDP) were studied in mice. CDDP was administered intraperitoneally to two groups (CDDP + Allop group and CDDP + CMC-Na group) at single doses of 10 mg/kg, and mice were sacrificed 3 days after CDDP administration. The body weights of the CDDP-administered group gradually decreased to approximately 78% of the values of the control group (saline + Allop group and saline + CMC-Na group) within 3 days. Plasma urea nitrogen and creatinine, especially in the CDDP + Allop group, increased after 3 days. Lipid peroxides in the blood and kidney were monitored by measuring the production of malondialdehyde (MDA), which increased in the CDDP + CMC-Na group. On the other hand, MDA levels in the CDDP + Allop group increased in the kidney but remained unchanged in the blood. Changes were observed in tissue glutathione (reduced form, GSH; oxidized form, GSSG) levels in the CDDP + Allop group but not in the CDDP + CMC-Na group. Histomorphological examination demonstrated the degeneration of the proximal tubuli in the CDDP-administered groups. Especially in the CDDP + Allop group, the increase of mesangium cells in the glomeruli was observed. From these results, it was suggested that Allop was not able to inhibit CDDP-induced lipid peroxidation in the kidney, and the kidney function became more severely impaired by the administration of Allop.
在小鼠中研究了别嘌醇（Allop）对一种抗肿瘤药物顺铂（CDDP）肾毒性中脂质过氧化的影响。将两组小鼠（CDDP + Allop组和CDDP + CMC-Na组）腹腔注射单剂量10 mg/kg的CDDP，并在给予CDDP 3天后处死小鼠。在3天内，给予CDDP组的体重逐渐下降至对照组（生理盐水 + Allop组和生理盐水 + CMC-Na组）体重值的约78%。3天后，血浆尿素氮和肌酐升高，尤其是在CDDP + Allop组。通过测量丙二醛（MDA）的生成来监测血液和肾脏中的脂质过氧化物，在CDDP + CMC-Na组中MDA增加。另一方面，CDDP + Allop组中肾脏的MDA水平升高，但血液中的MDA水平保持不变。在CDDP + Allop组中观察到组织谷胱甘肽（还原型，GSH；氧化型，GSSG）水平的变化，而在CDDP + CMC-Na组中未观察到。组织形态学检查显示给予CDDP组近端小管发生变性。特别是在CDDP + Allop组中，观察到肾小球系膜细胞增多。从这些结果表明，Allop不能抑制CDDP诱导的肾脏脂质过氧化，并且给予Allop会使肾功能受损更严重。
