A study of the nephrotoxicity of three cephalosporins in rabbits using 1H NMR spectroscopy.
Male New Zealand White rabbits received a single intravenous injection of 125 mg/kg cephaloridine, 500 mg/kg cefoperazone or 1000 mg/kg cephalothin. Histological examination of kidneys at 48 h post-dose confirmed the presence of bilateral necrosis of the proximal convoluted tubules in the cephaloridine-treated animals. 1H-NMR urinalysis of cephaloridine-treated rabbits detected drug-related resonances, decreased hippurate and increased glucose at 0-24 h post-dose accompanied by elevated levels of lactate, glycine, citrate, glutamine/glutamate and alanine at 24-48 h post-dose. No histopathological changes were observed following administration of cefoperazone or cephalothin. 1H-NMR spectra of urine collected from these animals showed drug-related resonances and decreased hippurate levels at 0-24 h post-dose, and increased glucose levels at 24-48 h post-dose. Analysis of urine by conventional clinical-chemistry failed to reveal any statistically significant differences between the treatment groups. Under the conditions of this study, the nephrotoxic effects of cephaloridine and the minimal effects of cefoperazone and cephalothin could be clearly distinguished by 1H-NMR urinalysis but not by conventional urinalysis.
Department of Toxicology, Sterling Winthrop Pharmaceuticals Research Division, Alnwick, Northumberland, UK.
S
S
Halligan
S J
SJ
Byard
A J
AJ
Spencer
T J
TJ
Gray
E S
ES
Harpur
F W
FW
Bonner
D000409:Alanine / Q000652:urine; D000818:Animals; D002438:Cefoperazone / Q000008:administration & dosage / Q000633:toxicity; D002509:Cephaloridine / Q000008:administration & dosage / Q000633:toxicity; D002511:Cephalosporins / Q000008:administration & dosage / Q000633:toxicity*; D002512:Cephalothin / Q000008:administration & dosage / Q000633:toxicity; D002951:Citrates / Q000652:urine; D019343:Citric Acid; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000652:urine; D005998:Glycine / Q000652:urine; D006029:Glycosuria / Q000652:urine; D006626:Hippurates / Q000652:urine; D007275:Injections, Intravenous; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D007773:Lactates / Q000652:urine; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011817:Rabbits; D016482:Urinalysis / Q000592:standards
D002511:Cephalosporins; D002951:Citrates; D006626:Hippurates; D007773:Lactates; D019343:Citric Acid; D019344:Lactic Acid; D018698:Glutamic Acid; D002438:Cefoperazone; D002509:Cephaloridine; D000409:Alanine; D002512:Cephalothin; C030514:hippuric acid; D005998:Glycine