Effects of ureteral obstruction on the toxicity of cephalosporins in the rabbit kidney.
The nephrotoxicity of the cephalosporin antibiotics is closely related to their secretory transport into the proximal tubular cell at the antiluminal (blood) site. The present report describes the effects of transient ureteral obstruction, which increases intracellular concentrations of secreted organic anions, on the cortical uptake and the proximal tubular toxicity of several cephalosporins given in mildly toxic doses. Unilateral obstruction for 1-2 hr increased the cytotoxicity of cephaloglycin and cefaclor, both of which are rapidly secreted across the tubular cell, but not of cephaloridine, which undergoes minimal secretion. Bilateral obstruction significantly increased the toxicity of cefaclor, which is rapidly secreted, but not of cefazolin, which is slowly secreted. Finally, there was a further augmentation of the effects of obstruction on the toxicity of cefaclor by a minimally toxic pretreatment regimen of neomycin. Studies of cortical antibiotic concentrations support the conclusion that the effects on toxicity are largely the result of the increased intracellular accumulation that results from obstruction.
D000818:Animals; D002433:Cefaclor / Q000633:toxicity; D002437:Cefazolin / Q000633:toxicity; D002507:Cephaloglycin / Q000633:toxicity; D002509:Cephaloridine / Q000633:toxicity; D002511:Cephalosporins / Q000378:metabolism / Q000633:toxicity*; D003250:Constriction; D005260:Female; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D009336:Necrosis; D009355:Neomycin / Q000494:pharmacology; D011817:Rabbits; D014513:Ureter
D002511:Cephalosporins; D002433:Cefaclor; D009355:Neomycin; D002437:Cefazolin; D002509:Cephaloridine; D002507:Cephaloglycin