Dieni Christopher Anthony, Callaghan Neal Ingraham, Gormley Patrick Thomas, Butler Kathryn Marie Alison, Maccormack Tyson James
Department of Chemistry and Biochemistry, Mount Allison University, Barclay Chemistry Building, 63C York Street, Sackville, New Brunswick E4L 1G8, Canada.
Department of Chemistry and Biochemistry, Mount Allison University, Barclay Chemistry Building, 63C York Street, Sackville, New Brunswick E4L 1G8, Canada.
Comp Biochem Physiol C Toxicol Pharmacol. 2014 May;162:51-61. doi: 10.1016/j.cbpc.2014.03.009. Epub 2014 Apr 3.
Liver toxicity of commercially relevant zinc oxide nanoparticles (nZnO) was assessed in a benthic freshwater cypriniform, the white sucker (Catostomus commersonii). Exposure to nZnO caused several changes in levels of liver enzyme activity, antioxidants, and lipid peroxidation end products consistent with an oxidative stress response. Aconitase activity decreased by ~65% but tended to be restored to original levels upon supplementation with Fe(2+), indicating oxidative inactivation of the 4Fe-4S cluster. Furthermore, glucose-6-phosphate dehydrogenase activity decreased by ~29%, and glutathione levels increased by ~56%. Taken together, these suggest that nZnO induces hepatic physiological stress. Each assay was then validated by using a single liver homogenate or plasma sample that was partitioned and treated with nZnO or Zn(2+), the breakdown product of nZnO. It was found that Zn(2+), but not nZnO, increased detected glutathione reductase activity by ~14% and decreased detected malondialdehyde by ~39%. This indicates that if appreciable nZnO dissolution occurs in liver samples during processing and assay, it may skew results, with implications not only for this study, but also for a wide range of nanotoxicology studies focusing on nZnO. Finally, in vitro incubations of cell-free rat blood plasma with nZnO failed to generate any significant increase in malondialdehyde or protein carbonyl levels, or any significant decrease in ferric reducing ability of plasma. This suggests that at the level tested, any oxidative stress caused by nZnO is the result of a coordinated physiological response by the liver.
在底栖淡水鲤形目鱼类——白亚口鱼（Catostomus commersonii）中评估了具有商业相关性的氧化锌纳米颗粒（nZnO）的肝脏毒性。暴露于nZnO会导致肝脏酶活性、抗氧化剂和脂质过氧化终产物水平发生多种变化，这与氧化应激反应一致。乌头酸酶活性下降了约65%，但在补充Fe(2+)后倾向于恢复到原始水平，表明4Fe-4S簇发生了氧化失活。此外，葡萄糖-6-磷酸脱氢酶活性下降了约29%，谷胱甘肽水平增加了约56%。综合来看，这些表明nZnO会诱导肝脏生理应激。然后，通过使用单个肝脏匀浆或血浆样本进行验证，该样本被分割并用nZnO或nZnO的分解产物Zn(2+)处理。结果发现，Zn(2+)而非nZnO使检测到的谷胱甘肽还原酶活性增加了约14%，并使检测到的丙二醛减少了约39%。这表明，如果在处理和检测过程中肝脏样本中发生了可观的nZnO溶解，可能会使结果产生偏差，这不仅对本研究有影响，而且对广泛的关注nZnO的纳米毒理学研究也有影响。最后，将无细胞大鼠血浆与nZnO进行体外孵育，未能使丙二醛或蛋白质羰基水平有任何显著增加，也未使血浆的铁还原能力有任何显著降低。这表明在所测试的水平下，nZnO引起的任何氧化应激都是肝脏协调生理反应的结果。
