Chromium is a catalytic metal able to foster oxidant damage, albeit its capacity to induce human LDL oxidation is to date unkown. Thus, we have investigated whether trivalent and hexavalent chromium, namely Cr(III) and Cr(VI), can induce human LDL oxidation. Cr(III) as CrCl3 is incapable of inducing LDL oxidation at pH 7.4 or 4.5. However, Cr(III), specifically at physiological pH of 7.4 and in the presence of phosphates, causes an absorbance increase at 234 resembling a spectrophotometric kinetics of LDL oxidation with a lag- and propagation-like phase. In this regard, it is conceivable that peculiar Cr(III) forms such as Cr(III) hydroxide and, especially, Cr(III) polynuclear hydroxocomplexes formed at pH 7.4 interact with phosphates generating species with an intrinsic absorbance at 234 nm, which increases over time resembling a spectrophotometric kinetics of LDL oxidation. Cr(VI), as K2Cr2O7, can instead induce substantial human LDL oxidation at acidic pH such as 4.5, which is typical of the intracellular lysosomal compartment. LDL oxidation is related to binding of Cr(VI) to LDL particles with quenching of the LDL tryptophan fluorescence, and it is inhibited by the metal chelators EDTA and deferoxamine, as well as by the chain-breaking antioxidants butylated hydroxytoluene and probucol. Moreover, Cr(VI)-induced LDL oxidation is inhibited by mannitol conceivably by binding Cr(V) formed from LDL-dependent Cr(VI) reduction and not by scavenging hydroxyl radicals (OH); indeed, the OH scavengers sodium formate and ethanol are ineffective against Cr(VI)-induced LDL oxidation. Notably, heightened LDL lipid hydroperoxide levels and decreased LDL tryptophan fluorescence occur in Cr plating workers, indicating Cr-induced human LDL oxidation in vivo. The biochemical, pathophysiological and clinical implications of these novel findings on chromium and human LDL oxidation are discussed.

中文翻译：

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铬与人低密度脂蛋白的氧化作用。

铬是一种催化金属，能够促进氧化剂的破坏，尽管迄今为止其诱导人类低密度脂蛋白氧化的能力尚不明确。因此，我们研究了三价铬和六价铬，即Cr（III）和Cr（VI）是否可以诱导人LDL氧化。作为CrCl3的Cr（III）在pH 7.4或4.5下不能诱导LDL氧化。但是，Cr（III），特别是在7.4的生理pH值和存在磷酸盐的情况下，会导致234处的吸光度增加，类似于具有滞后相和扩散相的LDL氧化的分光光度动力学。在这方面，可以想象到，特殊的Cr（III）形式，例如氢氧化Cr（III），尤其是在pH 7.4下形成的Cr（III）多核羟基复合物与磷酸盐相互作用，产生了在234 nm具有固有吸光度的物质，随时间增加，类似于LDL氧化的分光光度动力学。Cr（VI）作为K2Cr2O7，可以代替它在酸性pH（例如4.5）下诱导人体LDL大量氧化，这是细胞内溶酶体区室的典型特征。LDL氧化与Cr（VI）与LDL粒子的结合以及LDL色氨酸荧光的猝灭有关，并且被金属螯合剂EDTA和去铁胺以及链断裂抗氧化剂丁基化羟基甲苯和普罗布考抑制。此外，甘露醇可以抑制Cr（VI）诱导的LDL氧化，其结合方式是结合LDL依赖的Cr（VI）还原形成的Cr（V），而不是清除羟基（OH）。实际上，OH清除剂甲酸钠和乙醇对Cr（VI）诱导的LDL氧化无效。尤其，Cr电镀工人中LDL脂质氢过氧化物水平升高，LDL色氨酸荧光降低，这表明Cr在体内可诱导人LDL氧化。这些新发现对铬和人类低密度脂蛋白氧化的生化，病理生理学和临床意义进行了讨论。