Aryl Hydrocarbon Receptor and Dioxin-Related Health Hazards—Lessons from Yusho

Abstract

Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho.

Origin, dietary exposure, and toxicity of endocrine-disrupting food chemical contaminants: A comprehensive review

“…According to Stockholm Convention and US EPA, PCDDs and PCDFs, have been considered persistent organic pollutants (POPs), meaning they take a long time to decompose in the environment [ 34 ]. In western Japan in 1968, more than 2000 residents were intoxicated by the consumption of edible rice bran oil, which was polluted with high concentrations of PCDFs, PCDDs, and PCBs [ 35 ].…”

“…During Vietnam. War from 1961 to 1971, spreading the TCDD-contaminated Pesticides (Agent Orange) was linked to a high cancer mortality rate in 2005 [ 35 ].…”

The Association between Objective Tongue Color and the Static Blood Findings of Yusho Patients

“…It has been proposed that oxidative stress is one of the pathogenic factors for SB [12,13]. Dioxins and their related organochlorines are well-known environmental pollutants which induce oxidative stress [18]. These compounds bind arylhydrocarbon receptor and generate excessive amounts of reactive oxygen species [18].…”

“…Dioxins and their related organochlorines are well-known environmental pollutants which induce oxidative stress [18]. These compounds bind arylhydrocarbon receptor and generate excessive amounts of reactive oxygen species [18]. In fact, biomarkers for oxidative stress are elevated in the blood and urine of patients with Yusho who were intoxicated by high concentrations of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) [18][19][20].…”

“…These compounds bind arylhydrocarbon receptor and generate excessive amounts of reactive oxygen species [18]. In fact, biomarkers for oxidative stress are elevated in the blood and urine of patients with Yusho who were intoxicated by high concentrations of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF) [18][19][20]. Hence, along with the findings of previous study that found keishibukuryogan to be effective for Yusho patients, we speculated that SB might be central to the pathology of Yusho patients.…”