Reduction of gentamicin nephrotoxicity by the concomitant administration of poly-l-aspartic acid and poly-l-asparagine in rats.

Abstract

Williams and Hottendorf (1985) recently reported that poly-l-aspartic acid (pAsp) and poly-l-asparagine (pAsn) inhibit gentamicin (G) binding to brush border membrane vesicles in vitro and protect from G-induced nephrotoxicity in vivo. A model of infused rats was used to check for the early tissue alterations induced by G in animals receiving either G alone or the combination G + pAsp or G + pAsn. The cortical tissue was analysed 2 h or 2 days after the end of a 12 h infusion for signs of i) lysosomal phospholipidosis due to interference of G on phospholipids catabolism assessed by both biochemical (measurement of sphingomyelinase activity and of the total phospholipids content in renal cortex) and morphological analysis and ii) tubular regeneration and peritubular cells infiltration subsequent to focal necroses. While no reduction of G cortical levels was detected, significant changes in these parameters showed that G + pAsp and G + pAsn caused less phospholipidosis than G alone. Thus pAsp and pAsn decrease the severity of the early renal alterations induces by G.