Quarum M L, Houghton D C, Gilbert D N, McCarron D A, Bennett W M
J Lab Clin Med. 1984 Jan;103(1):104-14.
Because calcium has been reported to modify gentamicin binding to its proximal tubular brush border membrane receptor, we studied the effects of dietary calcium loading and subsequent hypercalciuria on experimental gentamicin nephrotoxicity. Male Fischer 344 rats were fed one of two diets that were identical except for calcium carbonate content: normal (0.5%) and high (4%). The high-calcium diet made rats hypercalciuric but there were no differences between the two groups in inulin clearance, sodium or osmolar excretion, or serum calcium prior to gentamicin administration. Animals on both diets were treated with gentamicin, 20 mg/kg b.i.d., for periods of 3 to 21 days. Both groups developed acute renal failure, but animals on the high-calcium diet had less severe acute toxic injury, as evidenced by studies of inulin clearance, renal histology, and in vitro cortical uptake of NMN and PAH. Furthermore, calcium-loaded animals tended to have lower peak renal cortical gentamicin levels during the period of acute toxicity. The mechanism by which increased dietary calcium protects against gentamicin nephrotoxicity remains speculative. Calcium and gentamicin may compete for the same brush border receptor or alternatively parathyroid suppression may result in diminution in tubular cell membrane drug binding sites. The possibility that high-calcium diets exert a nonspecific salutory effect on proximal tubular cell integrity has not been excluded.
由于有报道称钙可改变庆大霉素与其近端肾小管刷状缘膜受体的结合，我们研究了饮食中钙负荷及随后的高钙尿症对实验性庆大霉素肾毒性的影响。雄性Fischer 344大鼠喂食两种除碳酸钙含量外完全相同的饮食之一：正常饮食（0.5%）和高钙饮食（4%）。高钙饮食使大鼠出现高钙尿症，但在给予庆大霉素之前，两组在菊粉清除率、钠或渗透压排泄或血清钙方面没有差异。两种饮食组的动物均接受庆大霉素治疗，剂量为20 mg/kg，每日两次，持续3至21天。两组均出现急性肾衰竭，但高钙饮食组的动物急性毒性损伤较轻，这在菊粉清除率、肾脏组织学以及NMN和PAH的体外皮质摄取研究中得到证实。此外，钙负荷动物在急性毒性期间的肾皮质庆大霉素峰值水平往往较低。饮食中钙增加预防庆大霉素肾毒性的机制仍属推测。钙和庆大霉素可能竞争相同的刷状缘受体，或者甲状旁腺抑制可能导致肾小管细胞膜药物结合位点减少。高钙饮食对近端肾小管细胞完整性产生非特异性有益作用的可能性尚未排除。
