Effect of 6-hydroxydopamine on gluconeogenesis in the rat renal cortex.

Abstract

1. In the present study, the effects of 6-hydroxydopamine (6-OHDA) on renal gluconeogenesis were investigated in vitro using rat renal cortical slices. Cisplatin, a known nephrotoxin, was used as a positive control. The working hypothesis for the present study was that 6-OHDA, as a reactive oxygen species-producing agent, could inhibit renal gluconeogenesis. 2. 6-Hydroxydopamine is used for chemical sympathectomy because it selectively destroys adrenergic nerve endings. Long-term use of levodopa causes a variety of side-effects in parkinsonian patients. 6-Hydroxydopamine has been reported to be present in the urine of parkinsonian patients on levodopa medication. The renal toxicity of endogenously formed 6-OHDA is a matter of concern in these patients. 3. In one series of experiments, renal cortical slices were incubated for 60 min in medium containing 0.5, 1.0, 2.08, 5.15, 10.30 or 20.60 mg/mL 6-OHDA at 37 degrees C under a 100% O2 atmosphere. In another series of experiments, renal cortical slices were incubated in medium containing 10.30 mg/mL 6-OHDA for 15, 30, 45, 60, 90 or 120 min or in 6-OHDA-free medium. 4. In a second series of experiments, renal cortical slices were incubated for 60 min in medium containing 0.25, 0.50, 0.75, 1.0, 1.25 or 1.50 mg/mL cisplatin at 37 degrees C under a 100% O2 atmosphere. In another set of experiments, renal cortical slices were incubated in medium containing 1 mg/mL cisplatin for 15, 30, 45, 60, 90 or 120 min or in a cisplatin-free medium. 5. The results of the studies in which slices were incubated in 6-OHDA-containing media indicate that 6-OHDA induced a time- and concentration-dependent decrease in renal gluconeogenesis. Therefore, 6-OHDA causes functional injury of renal proximal tubule cells responsible for renal gluconeogenesis, thus leading to nephrotoxicity.