Apostoli Pietro, Catalani Simona, Zaghini Anna, Mariotti Andrea, Poliani Pietro Luigi, Vielmi Valentina, Semeraro Francesco, Duse Sarah, Porzionato Andrea, Macchi Veronica, Padovani Alessandro, Rizzetti Maria Cristina, De Caro Raffaele
Department of Experimental and Applied Medicine, Section of Occupational Health and Industrial Hygiene, University of Brescia, Italy.
Exp Toxicol Pathol. 2013 Sep;65(6):719-27. doi: 10.1016/j.etp.2012.09.006. Epub 2012 Oct 12.
The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.
长期接触钴和铬对生物的不良影响已得到明确界定。过去，这种毒性在很大程度上是一个与职业环境中接触相关的工业问题。然而，最近的报告描述了金属假体释放的高浓度钴和铬所介导的一种特殊毒性，尤其是在接受髋关节置换的患者中。包括失明、失聪和周围神经病变在内的临床症状提示了一种特殊的神经嗜性。然而，对于这一过程的神经病理学基础知之甚少，且仍缺乏实验证据。我们在实验环境中对此问题进行了研究，使用新西兰白兔，对其进行重复静脉注射钴和铬，单独注射或联合注射。单独注射铬后，尽管血液和组织中铬含量很高，但未出现明显的临床或病理改变，而钴铬联合注射组和钴注射组的兔子表现出提示听觉和视觉系统毒性的临床症状。组织病理学检查显示，这些动物出现严重的视网膜和耳蜗神经节细胞减少，伴有视神经损伤和感觉性耳蜗毛细胞丧失。有趣的是，改变的严重程度与剂量和暴露时间有关。这些数据证实了我们之前对接触受损髋关节假体异常释放的钴和铬的患者严重听觉和视神经毒性的观察。此外，我们已确定介导神经毒性的主要元素是钴，尽管介导这种毒性的分子机制仍有待确定。
