Increasing dietary calcium moderates experimental gentamicin nephrotoxicity.
Increasing dietary calcium moderates experimental gentamicin nephrotoxicity.
复制标题
增加膳食钙可减轻实验性庆大霉素肾毒性。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
W. Bennett
中科院分区：
文献类型：
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作者：
M. Quarum;D. Houghton;D. Gilbert;D. McCarron;W. Bennett
由于有报道称钙可以改变庆大霉素与其近端管刷边界膜受体的结合，因此我们研究了膳食钙负荷和随后的高钙尿对实验性庆大霉素肾毒性的影响。雄性Fischer 344大鼠被喂食两种饮食中的一种，除了碳酸钙含量相同：正常（0.5%）和高（4%）。高钙饮食使大鼠出现高钙血症，但两组在庆大霉素给药前菊粉清除率、钠或渗透性排泄、血清钙方面没有差异。两种饲粮均给予庆大霉素20 mg/kg b.d，试验期3 ~ 21 d。两组均出现急性肾衰竭，但高钙饮食的动物急性毒性损伤较轻，这一点得到菊粉清除率、肾脏组织学和NMN和PAH体外皮质摄取研究的证实。此外，在急性毒性期间，钙负荷动物的肾皮质庆大霉素水平峰值往往较低。增加膳食钙对庆大霉素肾毒性的保护机制仍在推测中。钙和庆大霉素可能竞争相同的刷状边界受体，或者甲状旁腺抑制可能导致小管细胞膜药物结合位点的减少。不排除高钙饮食对近端小管细胞完整性产生非特异性有益作用的可能性。
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.