The influence of acetylcysteine (ac-cys) on cisplatin (CP) nephrotoxicity was investigated in female Wistar rats. Administration of 0.6 mg CP 100 g-1 body wt. was followed by oliguria and proteinuria, as well as a significant increase of blood urea nitrogen concentration. The i.p. administration of 0.6 mg CP 100 g-1 body wt. concomitantly with 100 mg ac-cys 100 g-1 body wt. s.c. completely abolished the nephrotoxic effects of CP. However, following this, the Pt concentration in kidney was decreased significantly by ac-cys treatment. This was caused by the enhanced urinary excretion of Pt. The same effect on CP nephrotoxicity appeared when CP and ac-cys were dissolved together in solution prior to injection. It could be shown that in this solution a ligand exchange reaction of CP by ac-cys started immediately, resulting in increased renal excretion and decreased Pt concentration in kidney. From our results we concluded that the protective effect of ac-cys on CP nephrotoxicity is based on the formation of a complex unsuitable for tubular reabsorption.

The influence of ascorbic acid (AA, 5 g/kg body weight) on chromate (Cr, 10 mg/kg) induced proteinuria, which is a sensitive parameter of its nephrotoxicity, was investigated in adult female Wistar rats. The concentrations of Cr and ascorbic acid (AA) were determined in renal tissue. Cr nephrotoxicity is related to its intracellular reduction from Cr(VI) to Cr(III). Proteinuria was completely prevented by enhancement of extracellular reduction of Cr(VI) to Cr(III) followed by rapid renal excretion when Cr and AA were given concomitantly. With an interval up to 1 h between Cr and AA, proteinuria was decreased probably by the radical scavenging function of AA. At an interval of 3 h AA enhanced Cr toxicity by increased intracellular Cr reduction. If the interval was increased to 5 h or if Cr was given 24 h after AA, no influence of AA could be detected. Our results confirm that AA is a very effective reductant of Cr which can influence Cr nephrotoxicity in very high concentrations. It depends on the interval between Cr and AA administration whether or not there is a beneficial effect of AA in Cr nephrotoxicity.

The influence of pretreatment with triiodothyronine (T3) on cisplatin (CP)-induced nephrotoxicity was investigated in 10- and 55-day-old rats. Triiodothyronine pretreatment enhanced CP proteinuria in young and adult rats, and increased blood urea nitrogen concentration in 55-day-old rats. As T3 decreased Pt concentrations in renal tissue, the enhanced nephrotoxicity of CP by T3 must have another mechanism. Enhanced CP nephrotoxicity is discussed in connection with an increase of glutathione concentration obtained in renal tissue as a consequence of T3 pretreatment.