Laboratorio de Toxicología Ambiental, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón intersección Paseo Tollocan s/n, Col. Residencial Colón, 50120, Toluca, Estado de México, Mexico.
Facultad de Medicina, Universidad Autónoma del Estado de México. Paseo Tollocan /Jesús Carranza s/n. Toluca, 50120, Toluca, Estado de México, Mexico.
Chemosphere. 2024 Sep;364:143012. doi: 10.1016/j.chemosphere.2024.143012. Epub 2024 Aug 3.
Due to its extensive use as a painkiller, anti-inflammatory, and immune modulatory agent, as well as its effectiveness in treating severe COVID-19, dexamethasone, a synthetic glucocorticoid, has gained attention not only for its impact on public health but also for its environmental implications. Various studies have reported its presence in aquatic environments, including urban waters, surface samples, sediments, drinking water, and wastewater effluents. However, limited information is available regarding its toxic effects on nontarget aquatic organisms. Therefore, this study aimed to investigate the mechanism of toxicity underlying dexamethasone-induced brain damage in the bioindicator Danio rerio following long-term exposure. Adult zebrafish were treated with environmentally relevant concentrations of dexamethasone (20, 40, and 60 ng L-1) for 28 days. To elucidate the possible mechanisms involved in the toxicity of the pharmaceutical compound, we conducted a behavioral test battery (Novel Tank and Light and Dark tests), oxidative stress biomarkers, acetylcholinesterase enzyme activity quantification, histopathological analysis, and gene expression analysis using qRT-PCR (p53, bcl-2, bax, caspase-3, nrf1, and nrf2).The results revealed that the pharmaceutical compound could produce anxiety-like symptoms, increase the oxidative-induced stress response, decrease the activity of acetylcholinesterase enzyme, and cause histopathological alterations, including perineuronal vacuolization, granular and molecular layers deterioration, cell swallowing and intracellular spaces. The expression of genes involved in the apoptotic process (p53, bax, and casp-3) and antioxidant defense (nrf1 and nrf2) was upregulated in response to oxidative damage, while the expression of the anti-apoptotic gene bcl-2 was down-regulated indicating that the environmental presence of dexamethasone may pose a threat to wildlife and human health.
由于地塞米松作为一种止痛药、消炎药和免疫调节剂的广泛应用，以及在治疗严重 COVID-19 方面的有效性，这种合成糖皮质激素不仅因其对公共卫生的影响而受到关注，还因其对环境的影响而受到关注。各种研究报告称，地塞米松存在于水生环境中，包括城市水域、地表水样本、沉积物、饮用水和废水排放物中。然而，关于其对非目标水生生物的毒性影响的信息有限。因此，本研究旨在探讨长期暴露于环境相关浓度的地塞米松（20、40 和 60 ng/L）后，地塞米松诱导斑马鱼大脑损伤的毒性机制。成年斑马鱼用环境相关浓度的地塞米松（20、40 和 60 ng/L）处理 28 天。为了阐明该药物化合物毒性的可能机制，我们进行了行为测试（新鱼缸和明暗测试）、氧化应激生物标志物、乙酰胆碱酯酶活性定量、组织病理学分析和 qRT-PCR 基因表达分析（p53、bcl-2、bax、caspase-3、nrf1 和 nrf2）。结果表明，该药物化合物可产生焦虑样症状，增加氧化应激反应，降低乙酰胆碱酯酶活性，并导致组织病理学改变，包括神经周隙空泡化、颗粒层和分子层退化、细胞吞噬和细胞内空间。参与凋亡过程的基因（p53、bax 和 casp-3）和抗氧化防御（nrf1 和 nrf2）的表达上调，表明环境中存在地塞米松可能对野生动物和人类健康构成威胁。
