Wallenborn J Grace, Evansky Paul, Shannahan Jonathan H, Vallanat Beena, Ledbetter Allen D, Schladweiler Mette C, Richards Judy H, Gottipolu Reddy R, Nyska Abraham, Kodavanti Urmila P
Department of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA.
Toxicol Appl Pharmacol. 2008 Oct 1;232(1):69-77. doi: 10.1016/j.taap.2008.05.025. Epub 2008 Jun 6.
Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this, healthy male WKY rats (12 weeks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 microg/m(3) of aerosolized zinc sulfate (ZnSO(4)), 5 h/day, 3 days/week for 16 weeks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl beta-D-glucosaminidase, gamma-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated small changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels induces cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease.
锌是大多数环境颗粒物（PM）中的常见金属，有人提出它是PM引起心血管健康不良影响的致病成分。锌也是一种必需金属，有可能引发许多生理和非生理变化。大多数毒理学研究使用的是高剂量锌。我们假设，亚慢性吸入环境相关水平的锌会使健康大鼠的心脏发生变化。为了验证这一点，将健康的雄性WKY大鼠（12周龄）仅通过鼻吸入暴露于过滤空气或10、30或100微克/立方米的雾化硫酸锌（ZnSO₄）中，每天5小时，每周3天，持续16周。在最后一次暴露后48小时进行尸检，以确保观察到的影响是由于长期暴露而非最后一次暴露所致。支气管肺泡灌洗液中的中性粒细胞或巨噬细胞计数、可灌洗细胞总数或酶活性水平（乳酸脱氢酶、N-乙酰-β-D-氨基葡萄糖苷酶、γ-谷氨酰转移酶）均未观察到显著变化，表明肺部影响极小。在心脏中，胞质谷胱甘肽过氧化物酶活性降低，而线粒体铁蛋白水平升高，琥珀酸脱氢酶活性降低，提示存在线粒体特异性效应。虽然未观察到心脏病理学变化，但心脏基因阵列分析表明参与细胞信号传导的基因有微小变化，这一模式与已知的锌效应一致。这些数据表明，吸入环境相关水平的锌会诱发心脏效应。虽然健康大鼠的变化很小，但这些变化在已有心血管疾病的个体中可能尤为重要。
