Amelioration of gentamicin nephrotoxicity by phospholipids.
The effect of phospholipids on gentamicin-induced nephrotoxicity was studied in Sprague-Dawley rats. Group 1a (5 rats) were given daily intraperitoneal injections of 100 mg/kg of gentamicin and sacrificed on day 7. Group 1b (10 rats) were similarly treated but were sacrificed on day 14. Group 2a (5 rats) were given 30 mg/kg of phospholipids for 6 days and sacrificed on day 7, serving as phospholipid controls. Group 2b (5 rats) were similarly treated, and from day 7 onwards daily intraperitoneal injections of 100 mg/kg of gentamicin were given while oral phospholipids were continued until the rats were sacrificed 7 days after gentamicin treatment. Group 2c (10 rats) were treated in the same manner as group 2b but the animals were sacrificed on day 28 after gentamicin treatment. Group 3 (10 rats) were given 30 mg/kg of phospholipids concurrently with intraperitoneal gentamicin injections and were sacrificed on day 28. Protein concentrations, N-acetyl-beta-glucosaminidase (NAG) activities and creatinine were measured in 24-h urine samples. Serum creatinine concentrations were measured in blood samples and 24-h creatinine clearance calculated. Gentamicin concentrations were determined in kidney tissues from which sections were also taken for light- and electron-microscopy. Results showed that gentamicin induced a marked increase in NAG and protein excretion, and a marked decrease in creatinine clearance with six rats succumbing to uraemia. Phospholipid treatment, whether started before or concurrently with gentamicin injections, reduced gentamicin-induced nephrotoxicity. The rats did not lose weight. Urinary excretion of NAG and protein was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Chan
M K
MK
Department of Medicine, University of Hong Kong, Queen Mary Hospital.
Chan
K W
KW
Ng
W L
WL
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D003404:Creatinine / Q000097:blood; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010743:Phospholipids / Q000494:pharmacology*; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats
D005839:Gentamicins; D010743:Phospholipids; D003404:Creatinine; D000118:Acetylglucosaminidase