Impairment of the renal p-aminohippurate transport induced by 6-hydroxydopamine.

Abstract

In this study, the effects of 6-hydroxydopamine (6-OHDA) on renal p-aminohippurate transport were investigated in-vitro using rat renal cortical slices. Cisplatin, a known nephrotoxin, was used as positive control. Renal cortical slices were incubated for 60 min in a cisplatin-containing medium (0.83-5.0 microM) at 37 degrees C under a 100% O(2) atmosphere. In another series of experiments, renal cortical slices were incubated in a 3.33 microM cisplatin-containing medium for 15-120 min or in a cisplatin-free medium. Subsequently, for each series of experiments, kidney slices were incubated at 25 degrees C for 90 min in a media containing p-aminohippurate. In a further series of experiments, renal cortical slices were incubated for 60 min in a 6-OHDA containing medium (3.125-100 microM) at 37 degrees C under a 100% O(2) atmosphere. In another series of experiments, renal cortical slices were incubated in a 50 microM 6-OHDA-containing medium for 15-120 min or in 6-OHDA-free medium. Subsequently, for each series of experiments, kidney slices were incubated at 25 degrees C for 90 min in a media containing p-aminohippurate. The results of this study where slices were incubated in 6-OHDA- or cisplatin-containing media indicate that both 6-OHDA and cisplatin induced a time- and concentration-dependent decrease in p-aminohippurate accumulation by renal cortical slices. Therefore, similarly to cisplatin, 6-OHDA causes functional injury of renal proximal tubule cells, leading to impairment of transport processes across the cell membrane.