Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Jeonnam, 57922, Republic of Korea.
Environ Geochem Health. 2023 Nov;45(11):8663-8683. doi: 10.1007/s10653-023-01746-x. Epub 2023 Sep 12.
The molecular mechanisms and associations of mixed heavy metals (lead, mercury, and cadmium) on obstructive lung function (OLF) in males and females remain unknown. Here, we evaluated the interaction between the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio and three common heavy metals in males and females (n = 6221). Molecular processes involved in OLF development caused by mixed heavy metals were also identified to corroborate the earlier findings. In both males and females, as well as across the entire population, we found that serum cadmium levels were inversely related to the FEV1/FVC ratio. Interactions between serum cadmium and lead, as well as cadmium and mercury, were observed in relation to the FEV1/FVC ratio. Additionally, we observed negative correlations between the FEV1/FVC ratio and mixed serum cadmium, lead, and mercury in both men and women as well as in the overall population. Seven genes were identified as contributing to the etiology of OLF and targeted by combined heavy metals in silico analysis (CYP1A1, CRP, CXCL8, HMOX1, IL6, NOS2, and TNF). The primary relationships between these genes were co-expression interactions. The significant transcription factors and miRNAs associated with OLF and a combination of the examined heavy metals were identified as NFKB2, hsa-miR-155-5p, and hsa-miR-203a-3p. The main biological processes involved in the emergence of OLF induced by mixed heavy metals were listed as inflammatory and oxidative stress pathways, lung fibrosis, chronic obstructive pulmonary disease, as well as cytokine activity, monooxygenase activity, oxidoreductase activity, and interleukin-8 production. Threshold estimations and miRNA sponge patterns for heavy metal exposure levels associated with OLF were evaluated for both males and females. This study found that cadmium plays the most important role in the mixture of cadmium, lead, and mercury in the pathogenesis of OLF. Future studies are required to verify our findings and uncover the molecular mechanisms of long-term exposure to a variety of heavy metals, especially cadmium, in other populations, including children, adolescents, and the elderly.
混合重金属（铅、汞和镉）对男性和女性阻塞性肺功能（OLF）的分子机制和关联尚不清楚。在这里，我们评估了一秒用力呼气量（FEV1）/用力肺活量（FVC）比值与男性和女性三种常见重金属之间的相互作用（n=6221）。还确定了涉及混合重金属引起的 OLF 发展的分子过程，以证实早期的发现。在男性和女性以及整个人群中，我们发现血清镉水平与 FEV1/FVC 比值呈负相关。在 FEV1/FVC 比值方面观察到血清镉与铅以及镉与汞之间的相互作用。此外，我们还观察到在男性和女性以及整个人群中，FEV1/FVC 比值与混合血清镉、铅和汞之间存在负相关。在计算机分析中，有 7 个基因被确定为 OLF 病因学的贡献者，并被联合重金属靶向（CYP1A1、CRP、CXCL8、HMOX1、IL6、NOS2 和 TNF）。这些基因之间的主要关系是共表达相互作用。确定了与 OLF 和所检查的重金属组合相关的重要转录因子和 miRNA，分别为 NFKB2、hsa-miR-155-5p 和 hsa-miR-203a-3p。与混合重金属引起的 OLF 相关的主要生物学过程被列为炎症和氧化应激途径、肺纤维化、慢性阻塞性肺疾病以及细胞因子活性、单加氧酶活性、氧化还原酶活性和白细胞介素-8 产生。为男性和女性评估了与 OLF 相关的重金属暴露水平的阈值估计和 miRNA 海绵模式。这项研究发现，镉在镉、铅和汞混合物引起的 OLF 发病机制中起着最重要的作用。需要进一步的研究来验证我们的发现，并揭示其他人群（包括儿童、青少年和老年人）长期暴露于各种重金属（尤其是镉）的分子机制。
