Polyaspartic Acid Prevents Experimental Aminoglycoside Nephrotoxicity

D. N. Gilbert; C. A. Wood; S. J. Kohlhepp; P. W. Kohnen; D. C. Houghton; H. C. Finkbeiner; J. Lindsley; W. M. Bennett

doi:10.1093/infdis/159.5.945

Polyaspartic Acid Prevents Experimental Aminoglycoside Nephrotoxicity

D. N. Gilbert, C. A. Wood, S. J. Kohlhepp, P. W. Kohnen, D. C. Houghton, H. C. Finkbeiner, J. Lindsley, W. M. Bennett

Pathology

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Abstract

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 <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.

Original language	English (US)
Pages (from-to)	945-953
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	159
Issue number	5
DOIs	https://doi.org/10.1093/infdis/159.5.945
State	Published - May 1989

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General Medicine

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title = "Polyaspartic Acid Prevents Experimental Aminoglycoside Nephrotoxicity",

abstract = "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 <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.",

author = "Gilbert, {D. N.} and Wood, {C. A.} and Kohlhepp, {S. J.} and Kohnen, {P. W.} and Houghton, {D. C.} and Finkbeiner, {H. C.} and J. Lindsley and Bennett, {W. M.}",

note = "Funding Information: This work was supported by a grant from the Pharmaceutical Researchand DevelopmentDivisionof the Bristol-MyerCompany.",

year = "1989",

month = may,

doi = "10.1093/infdis/159.5.945",

language = "English (US)",

volume = "159",

pages = "945--953",

journal = "Journal of Infectious Diseases",

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AU - Gilbert, D. N.

AU - Wood, C. A.

AU - Kohlhepp, S. J.

AU - Kohnen, P. W.

AU - Houghton, D. C.

AU - Finkbeiner, H. C.

AU - Lindsley, J.

AU - Bennett, W. M.

N1 - Funding Information: This work was supported by a grant from the Pharmaceutical Researchand DevelopmentDivisionof the Bristol-MyerCompany.

PY - 1989/5

Y1 - 1989/5

N2 - 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 <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.

AB - 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 <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.

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JO - Journal of Infectious Diseases

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Polyaspartic Acid Prevents Experimental Aminoglycoside Nephrotoxicity

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