Elliott W C, Parker R A, Houghton D C, Gilbert D N, Porter G A, DeFehr J, Bennett W M
Res Commun Chem Pathol Pharmacol. 1980 Jun;28(3):483-95.
To examine the possibility that gentamicin binding to renal tubular epithelium is electrostatic, the effect of sodium bicarbonate-induced alkaline diuresis and ammonium chloride administration on the course of gentamicin nephrotoxicity in male Fischer 344 rats was examined. After 14 days of gentamicin, sodium bicarbonate drinking animals did not differ significantly from tap water drinking controls in the degree of nephrotoxicity as determined by serum creatinine, in vitro para-aminohippurate and N-methylnicotinamide uptake, histology and renal cortical gentamicin concentrations. However, 7/10 sodium bicarbonate drinking animals had extensive intratubular renal calcifications as compared to 0/29 tap water drinkers. Ammonium chloride drinking animals had more severe toxicity than tap water drinking controls. We conclude that in our model, sodium bicarbonate administration does not reduce experimental gentamicin toxicity and is associated with intratubular calcification. Ammonium chloride potentiates gentamicin nephrotoxicity.
为了研究庆大霉素与肾小管上皮细胞的结合是否为静电结合,我们检测了碳酸氢钠诱导的碱性利尿和氯化铵给药对雄性Fischer 344大鼠庆大霉素肾毒性病程的影响。给予庆大霉素14天后,通过血清肌酐、对氨基马尿酸和N-甲基烟酰胺的体外摄取、组织学以及肾皮质庆大霉素浓度测定发现,饮用碳酸氢钠的动物与饮用自来水的对照动物在肾毒性程度上无显著差异。然而,与29只饮用自来水的动物中0只出现肾小管内广泛钙化相比,10只饮用碳酸氢钠的动物中有7只出现了这种情况。饮用氯化铵的动物比饮用自来水的对照动物毒性更严重。我们得出结论,在我们的模型中,给予碳酸氢钠并不能降低实验性庆大霉素毒性,且与肾小管内钙化有关。氯化铵会增强庆大霉素的肾毒性。