Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
Department of Chemical Engineering, Texas A&M University, College Station, TX, USA.
Crit Rev Toxicol. 2020 Jul;50(6):463-473. doi: 10.1080/10408444.2020.1773759. Epub 2020 Jun 29.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and structurally related halogenated aromatics modulate gene expression and induce biochemical and toxic responses that are mediated by initial binding to the aryl hydrocarbon receptor (AhR). The AhR also binds structurally diverse compound including pharmaceuticals, endogenous biochemicals, health-promoting phytochemicals, and microbial metabolites. Many of these AhR ligands do not induce TCDD-like toxic responses and some AhR ligands such as microbial metabolites of tryptophan play a role in maintaining gut health and protecting against intestinal inflammation and cancer. Many AhR ligands exhibit tissue- and response-specific AhR agonist or antagonist activities, and act as selective AhR modulators (SAhRMs) and this SAhRM-like activity has also been observed in AhR-ligand-mediated effects in the intestine. This review summarizes studies showing that several AhR ligands including phytochemicals and TCDD protect against dextran sodium sulfate-induced intestinal inflammation. In contrast, AhR ligands such as oxazole compounds enhance intestinal inflammation suggesting that AhR-mediated gut health can be enhanced or decreased by selective AhR modulators and this needs to be considered in development of AhR ligands for therapeutic applications in treating intestinal inflammation.
2,3,7,8-四氯二苯并对二恶英（TCDD，二恶英）和结构上相关的卤代芳烃调节基因表达，并诱导生化和毒性反应，这些反应是通过与芳烃受体（AhR）的初始结合介导的。AhR 还结合结构多样的化合物，包括药物、内源性生化物质、促进健康的植物化学物质和微生物代谢物。这些 AhR 配体中的许多不会诱导 TCDD 样毒性反应，而一些 AhR 配体，如色氨酸的微生物代谢物，在维持肠道健康和预防肠道炎症和癌症方面发挥作用。许多 AhR 配体表现出组织和反应特异性的 AhR 激动剂或拮抗剂活性，并作为选择性 AhR 调节剂（SAhRMs）发挥作用，这种 SAhRM 样活性也在 AhR 配体介导的肠道效应中观察到。本综述总结了几项研究表明，包括植物化学物质和 TCDD 在内的几种 AhR 配体可预防葡聚糖硫酸钠诱导的肠道炎症。相比之下，如恶唑类化合物等 AhR 配体则增强肠道炎症，这表明 AhR 介导的肠道健康可以通过选择性 AhR 调节剂增强或减弱，在开发用于治疗肠道炎症的 AhR 配体的治疗应用时需要考虑这一点。
