Aryl hydrocarbon receptorからみた油症の病態と治療開発2020

In 1968, more than 2,000 peoples were exposed to high concentrations of dioxin-like compounds by eating rice bran oil contaminated with 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), polychlorinated biphenyls, and polychlorinated quarter phenyls. These Yusho (oil disease in Japanese) patients have been suffered from various symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, hyperesthesia or numbness of extremities since then. The blood concentrations of 2,3,4,7,8-PeCDF, major causal agent for toxicity, are still very high in many Yusho patients even now. Dioxins exert their major toxicity by binding and activating arylhydrocarbon receptor (AHR) and subsequent generation of reactive oxygen species (ROS). In addition, recent studies have revealed a pathogenic role of AHR in manifestation of various Yusho symptoms. Moreover, medicinal agents which inhibit AHR activation and ROS production (antioxidative AHR inhibitor) may be applicable for the treatment of Yusho patients. In this review, we summarize current topics on Yusho and its therapeutic approach with special reference to AHR.