Features of gentamicin nephrotoxicity and effect of concurrent cephalothin in the rat.
Features of gentamicin nephrotoxicity and effect of concurrent cephalothin in the rat.
复制标题
庆大霉素肾毒性特点及并发头孢噻吩对大鼠的影响。
作者：
Sugarman,A;Brown,RS;Silva,P;Rosen,S
SD大鼠每日给予庆大霉素10~70 mg/kg，连续给药9天后，肾小球滤过率随剂量增加呈线性下降，并伴有急性肾小管坏死和管型形成的组织学改变。在这项研究中，肾毒性与庆大霉素的峰值水平相关，而不是与谷值相关，这表明随着时间的推移，庆大霉素的平均水平决定了肾脏损伤。庆大霉素引起的多尿主要是由肾小管浓缩缺陷引起的，而不是钠或渗透压排泄增加所致，可能是由于Henle环的髓质细肢的管型占优势所致。没有发现庆大霉素对皮质或髓质钠钾三磷酸腺苷酶活性的影响是适度的钠消耗的原因。同时给予头孢菌素钠降低了高剂量庆大霉素的肾毒性，这种作用不能用添加的钠或不可再吸收的阴离子解释。
Sprague-Dawley rats given gentamicin from 10 to 70 mg/kg/day for 9 days showed a linear decrease in glomerular filtration rate with increasing dose, paralleled by histologic changes of acute tubular necrosis and cast formation only at the higher doses. Nephrotoxicity was correlated with the peak, rather than trough, serum gentamicin levels in this study, suggesting that it is the mean level of gentamicin over time that determines renal injury. The polyuria caused by gentamicin resulted mainly from a tubular concentrating defect rather than enhanced sodium or osmolal excretion and may be explained by the finding of a predominance of casts in the medullary thin limbs of the loops of Henle. No effect of gentamicin on the activity of cortical or medullary sodium-potassium adenosine triphosphatase was found to account for the modest sodium wasting. Concurrent administration of sodium1cephalothin decreased the renal toxicity of gentamicin at high doses, an effect not explained by the added sodium or nonreabsorbable anion.