Smetana S, Khalef S, Kopolovic G, Bar-Khayim Y, Birk Y, Kacew S
Nephrology Unit, Wolfson Medical Center, Holon, Israel.
Ren Fail. 1992;14(2):147-53. doi: 10.3109/08860229209039124.
Daily intraperitoneal (i.p.) injection of genatmicin at a dose of 70 mg/kg for 11 days produced nephrotoxicity in female Sprague-Dawley rats as evidenced by increased excretion of urinary protein and trypsin inhibitory activity as well as rise in renal individual class and total phospholipid. The observed proteinuria was associated with a significant twofold fall in creatinine clearance and histopathological changes, including the presence of hyaline casts and flattened epithelial cells within the lumen of proximal convoluted tubules. Although pyridoxal-5-phosphate (50 mg/kg) administered i.p. did not significantly alter creatinine clearance, histopathology, proteinuria, and urinary trypsin inhibitory activity, an increase in individual class and total phospholipid was noted in kidney. In rats simultaneously administered gentamicin and pyridoxal-5-phosphate, the observed fall in renal gentamicin content was associated with a return of individual class and total phospholipid to control values. However, the decline in creatinine clearance, enhanced proteinuria, and increase in urinary trypsin inhibitory activity in the simultaneous-treated group was similar or greater than that seen in the gentamicin-only injected rats. Morphological examination of simultaneous-treated rats revealed extensive alterations in proximal tubules including numerous mitotic figures, large vesicular nucleii, and prominent nucleoli in epithelial cells as well as hyaline casts within the lumen. Our data combined with results of previous studies suggest that sex and type of rat strain are important factors in aminoglycoside-induced nephrotoxicity. It is evident that a specific concentration of pyridoxal-5-phosphate may be necessary to provide protection against all manifestations of aminoglycoside-induced renal damage.
对雌性斯普拉格 - 道利大鼠每日腹腔注射70毫克/千克剂量的庆大霉素，持续11天，可导致肾毒性，表现为尿蛋白排泄增加、胰蛋白酶抑制活性增加以及肾单个类别和总磷脂含量升高。观察到的蛋白尿与肌酐清除率显著下降两倍以及组织病理学变化有关，包括近端曲管腔内出现透明管型和扁平上皮细胞。尽管腹腔注射磷酸吡哆醛（50毫克/千克）并未显著改变肌酐清除率、组织病理学、蛋白尿和尿胰蛋白酶抑制活性，但在肾脏中观察到单个类别和总磷脂有所增加。在同时给予庆大霉素和磷酸吡哆醛的大鼠中，观察到肾脏中庆大霉素含量下降，同时单个类别和总磷脂恢复到对照值。然而，同时治疗组中肌酐清除率的下降、蛋白尿增加以及尿胰蛋白酶抑制活性增加与仅注射庆大霉素的大鼠相似或更严重。对同时治疗大鼠的形态学检查显示近端小管有广泛改变，包括上皮细胞中有许多有丝分裂图像、大泡状核仁和突出的核仁以及管腔内的透明管型。我们的数据与先前研究结果相结合表明，大鼠品系的性别和类型是氨基糖苷类药物诱导肾毒性的重要因素。显然，可能需要特定浓度的磷酸吡哆醛来预防氨基糖苷类药物诱导的肾损伤的所有表现。
