Polyaspartic acid protects against gentamicin nephrotoxicity in the rat.
Polyamino acids including polyaspartic acid (PAA) have been reported to provide protection against the development of aminoglycoside-induced nephrotoxicity in the rat as assessed by histopathology scoring. We sought to confirm and extend these observations by determining whether PAA also prevented functional and biochemical lesions of gentamicin-nephrotoxicity in an animal model studied extensively in our laboratory. Rats were given injections of: 1) 0.9% NaCl at 2.5 ml/kg b.wt. per day; 2) PAA (mol.wt. 15,000) at 500 mg/kg per day; 3) gentamicin at 100 mg/kg per day or 4) gentamicin at 100 mg/kg per day and PAA at 500 mg/kg per day for 6 days. Rats injected with gentamicin exhibited: 1) increased urinary excretion of the brush border membrane enzyme alanine aminopeptidase and the lysosomal enzyme N-acetyl-beta-d-glucosaminidase after the first injection; 2) increased total phospholipid and malondialdehyde but decreased catalase activity in the renal cortex; 3) elevation of serum creatinine and depression of creatinine clearance and 4) extensive proximal tubular cell necrosis all determined 24 hr after the last injection of gentamicin. Rats injected with gentamicin plus PAA also exhibited increased urinary excretion of alanine aminopeptidase not different in magnitude from that of rats injected with gentamicin alone, whereas N-acetyl-beta-d-glucosaminidase rose more slowly and returned to base line by day 4. Total renal cortical phospholipid was elevated to the same extent in the two groups. Malondialdehyde was not different from control and catalase activity was significantly less depressed in rats injected with gentamicin plus PAA.(ABSTRACT TRUNCATED AT 250 WORDS)
Ramsammy
L S
LS
Department of Internal Medicine, State University of New York, Stony Brook.
Josepovitz
C
C
Lane
B P
BP
Kaloyanides
G J
GJ
D000818:Animals; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D005839:Gentamicins / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D005839:Gentamicins; D010455:Peptides; C017645:polyaspartate; D008315:Malondialdehyde; D003404:Creatinine; D002374:Catalase