Inhibition of renal membrane binding and nephrotoxicity of gentamicin by polyasparagine and polyaspartic acid in the rat.

The effect of the polyamino acids, polylysine, polyasparagine and polyaspartic acid, on 3H-gentamicin binding to rat renal brush border membranes was observed. All three polyamino acids showed inhibition of 3H-gentamicin binding at 1X and 0.1X the molar amount of gentamicin. Polylysine, polyasparagine and polyaspartic acid were subsequently tested in vivo for potential nephroprotective activity vs. gentamicin in a 14-day subacute nephrotoxicity model at 3X, 0.5X and 0.3X the molar dose of gentamicin, respectively. While polylysine did not produce significant nephroprotection, polyasparagine and polyaspartic acid completely eliminated gentamicin-induced nephrotoxicity.