Appenroth D, Winnefeld K, Schröter H, Rost M
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany.
Arch Toxicol. 1994;68(2):138-41. doi: 10.1007/s002040050047.
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.
在成年雌性Wistar大鼠中,研究了抗坏血酸(AA,5克/千克体重)对铬(Cr,10毫克/千克)诱导的蛋白尿的影响,蛋白尿是铬肾毒性的一个敏感参数。测定了肾组织中铬和抗坏血酸(AA)的浓度。铬的肾毒性与其从六价铬(Cr(VI))细胞内还原为三价铬(Cr(III))有关。当同时给予铬和AA时,通过增强细胞外六价铬(Cr(VI))还原为三价铬(Cr(III))并随后快速经肾排泄,蛋白尿完全得到预防。铬和AA之间间隔长达1小时时,蛋白尿可能因AA的自由基清除功能而减少。间隔3小时时,AA通过增加细胞内铬的还原增强了铬的毒性。如果间隔增加到5小时,或者在给予AA 24小时后给予铬,则未检测到AA的影响。我们的结果证实,AA是一种非常有效的铬还原剂,在非常高的浓度下可以影响铬的肾毒性。AA对铬肾毒性是否有有益作用取决于铬和AA给药之间的间隔。