Protective effect of N-acyl amino acids (NAAs) on cephaloridine (CER) nephrotoxicity in rabbits.
The protective effect of N-acyl amino acids (NAAs) against cephaloridine (CER)-induced nephrotoxicity was studied in rabbits. A large single intravenous dose of CER (more than 100 mg/kg) induced severe proximal tubular necrosis. Simultaneous treatment with several NAAs (at dosages of 100, 200 mg/kg, etc., i.v.), such as N-benzoyl-beta-alanine (NBBA), N-benzoyl-6-aminocaproic acid, and N alpha,epsilon-dibenzoyl-D,L-lysine, remarkably suppressed the histopathological damage in the kidney induced by CER. NAAs have generally low toxicity in laboratory animals (e.g., the LD50 of NBBA was more than 3,000 mg/kg, i.v. in rats), and NAAs were suggested to be good candidates for reducing the nephrotoxicity of CER and other beta-lactam antibiotics.
Hirouchi
Y
Y
Product Development Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Naganuma
H
H
Kawahara
Y
Y
Okada
R
R
Kamiya
A
A
Inui
K
K
Hori
R
R
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002509:Cephaloridine / Q000008:administration & dosage / Q000633:toxicity*; D006651:Histocytochemistry; D007275:Injections, Intravenous; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D011817:Rabbits; D013194:Staining and Labeling
D000596:Amino Acids; C047207:N-benzoylalanine; D002509:Cephaloridine; D000409:Alanine