Polyaspartic acid prevents experimental aminoglycoside nephrotoxicity.
The influence of the polyamino acid polyaspartic acid (PAA) on experimental aminoglycoside nephrotoxicity was determined. PAA prevented all measured functional and pathologic evidence of gentamicin nephrotoxicity for less than or equal to 27 d of study. All the animals given PAA, either alone or with gentamicin, developed prominent cytoplasmic vacuoles in the cells of the renal proximal convoluted tubules; the vacuoles in rats given just PAA differed from those observed in rats given PAA plus gentamicin. Rats given PAA plus gentamicin accumulated roughly 10 times more renal aminoglycoside as did rats given gentamicin alone. Immunohistochemical localization studies confirmed the presence of increased amounts of gentamicin in the cytoplasm of the tubular cells of animals given gentamicin plus PAA. PAA did not alter the in vitro antimicrobial activity of gentamicin versus Escherichia coli or Pseudomonas aeruginosa. These studies demonstrate the ability of PAA to prevent experimental gentamicin nephrotoxicity.
Gilbert
D N
DN
Chiles Research Institute, Providence Medical Center, Portland, OR 97213.
Wood
C A
CA
Kohlhepp
S J
SJ
Kohnen
P W
PW
Houghton
D C
DC
Finkbeiner
H C
HC
Lindsley
J
J
Bennett
W M
WM
D000818:Animals; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000032:analysis / Q000627:therapeutic use / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007668:Kidney / Q000032:analysis / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D010455:Peptides / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D005839:Gentamicins; D010455:Peptides; C017645:polyaspartate