蒽,多环芳烃(PAH),是一种广泛存在的环境污染物,对人类健康构成潜在风险。暴露于蒽会导致各种不利的健康影响,包括皮肤相关疾病.光暴露从环境中充分去除蒽,但也产生更多的降解产物,其可能更具毒性。本研究的目的是评估由光降解引起的蒽皮毒性的变化,并了解这种变化的机理。在本研究中,超过99.99%的蒽在24小时内降解,同时生产许多中间产品,包括9,10-蒽醌和邻苯二甲酸。将具有不同曝光持续时间的蒽产品应用于2D和3D人角质形成细胞培养物。虽然未降解的蒽显著延缓了细胞迁移,在光降解蒽的存在下,细胞的活力和分化急剧下降。与对照细胞相比,蒽光降解产物还改变了许多炎症相关基因的表达模式。在这些基因中,il1a,il1b,il8,cxcl2,s100a9和mmp1被上调,而tlr4和mmp3被光降解的蒽下调。光降解和非降解蒽向无毛小鼠背部皮肤的局部递送显示出光降解蒽的更多毒性作用。蒽的4小时光降解产物增厚了表皮层,增加皮肤细胞,并诱导炎症标志物的上调,il1a,il1b,s100a9和mmp1。此外,它还阻止了间隙连接蛋白的产生,Connexin-43.所有证据表明,光降解会增强蒽对皮肤的毒性。蒽的4小时光降解产物导致类似于急性炎症性皮肤病的临床症状,如特应性和接触性皮炎,湿疹,牛皮癣。因此,当个体暴露于PAHs时,也应考虑蒽对皮肤刺激的潜在风险,尤其是在阳光强烈的环境中。
Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to
anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in
anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded
anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded
anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.