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.
D000818:Animals; D005839:Gentamicins / Q000378:metabolism / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins; D010455:Peptides; D011107:Polylysine; C017645:polyaspartate; C045164:polyasparagine