Optimal dosage and early intervention of L-ascorbic acid inhibiting K2Cr2O7-induced renal tubular cell damage

Abstract

Chromium poisoning can cause renal failure and death. Chromium intoxication may be managed using L-ascorbic acid (vitamin C) therapy. However, the evidence supporting the effectiveness of this treatment is insufficient, and the mechanism of action has not been clarified in renal cells. In this study, our results showed that the optimal regimen of L-ascorbic acid therapy in human epithelial renal proximal tubule cells, HK-2 cells, was 30 μg/mL. Supplementation of L-ascorbic acid with 30 μg/mL and within 8 h of chromium intoxication (K₂Cr₂O_7, Cr⁶⁺) was effective to inhibit renal tubular cell damage by blocking generation of free radicals, cell apoptosis, and autophagy. Intracellular chromium concentrations were estimated using electrothermal atomic absorption spectrometry. Treatment of L-ascorbic acid within 8 h of chromium intoxication significantly decreased the entry of chromium into the cells. Moreover, concomitant administration of L-ascorbic acid with repeatedly dosing at 8-hourly intervals had a better protective effect at lower concentration of L-ascorbic acid when compared to single dosing of L-ascorbic acid at an early time point of chromium intoxication. These findings might help physicians develop effective therapy strategies in renal failure.

Keywords: Apoptosis; Ascorbic acid; Autophagy; Chromium(Cr(6+)); Nephrotoxicity; Vitamin C.