1H-NMR spectroscopy as a means of monitoring nephrotoxicity as exemplified by studies with cephaloridine.
1. Male albino rats were dosed intravenously with either 0.9% saline or cephaloridine in saline at doses of 650, 750 or 950 mg kg-1 d-1 for 7 d. 2. Urine analysis on day 3, after two doses of cephaloridine showed dose-related increases in glucose, total protein, N-acetyl beta-D-glucosaminidase, gamma-glutamyltranspeptidase, alkaline phosphatase and lactate dehydrogenase. 1H-NMR spectroscopy showed corresponding disturbed profiles of products of intermediary metabolism indicative of a disruption of renal function. 3. By day 6, after five doses of cephaloridine, analysis by both 1H-NMR and conventional methods showed that all indices had returned to normal. 1H-NMR was demonstrated to provide useful complementary information to conventional techniques on the time course of the onset of the nephrotoxicity and the recovery phase, and was at least as sensitive as conventional urine analysis.
ICI Pharmaceuticals Safety of Medicines Department, Alderley Park, Macclesfield, UK.
L B
LB
Murgatroyd
R J
RJ
Pickford
I K
IK
Smith
I D
ID
Wilson
B J
BJ
Middleton
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002509:Cephaloridine / Q000633:toxicity* / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002509:Cephaloridine