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L-抗坏血酸抑制 KCrO4 诱导的肾小管细胞损伤的最佳剂量和早期干预。

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

机构信息

Emergency Department, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Family Medicine Department, Taoyuan Branch, Taipei Veterans General Hospital, Taipei, Taiwan.

Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

J Trace Elem Med Biol. 2018 Jul;48:1-7. doi: 10.1016/j.jtemb.2018.02.022. Epub 2018 Mar 2.

DOI:10.1016/j.jtemb.2018.02.022
PMID:29773167
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 (KCrO Cr) 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.

摘要

铬中毒可导致肾衰竭和死亡。铬中毒可以使用 L-抗坏血酸(维生素 C)治疗。然而,这种治疗方法的有效性的证据不足,并且其在肾细胞中的作用机制尚未阐明。在这项研究中,我们的结果表明,L-抗坏血酸治疗人肾小管上皮细胞 HK-2 细胞的最佳方案为 30μg/mL。在铬中毒(KCrO Cr)后 8 小时内补充 30μg/mL 的 L-抗坏血酸,可通过阻断自由基生成、细胞凋亡和自噬来有效抑制肾小管细胞损伤。用电热原子吸收光谱法估计细胞内铬浓度。铬中毒后 8 小时内用 L-抗坏血酸治疗可显著减少铬进入细胞。此外,与早期单次给予 L-抗坏血酸相比,L-抗坏血酸在铬中毒早期多次给予,每 8 小时给予一次,在较低浓度的 L-抗坏血酸时具有更好的保护作用。这些发现可能有助于医生制定肾衰竭的有效治疗策略。

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