DENG YUQI

BACKGROUND: Exposure to arsenic increases the risk of hypertension. Indeed, a high level of arsenic in human serum, a reliable biomarker of arsenic exposure, was shown to be linked to increased prevalence of hypertension among a study of Japanese residents. However, no beneficial food that decreases the risk of arsenic-mediated hypertension has been determined by considering intake scores of multiple foods. METHODS: The comprehensive effects of combined beverage intake on the risk of hypertension, mediated by decreased levels of total arsenic in fasting serum, were investigated among the same group of 2706 residents. RESULTS: Our generalized linear regression analysis for each beverage showed significant negative associations of serum arsenic levels with milk and vegetable juice intake scores among 11 beverages. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) analyses of combined beverage intake scores reveal that milk was the beverage most strongly associated with lower serum arsenic levels. Subsequent causal mediation analysis further showed that increased milk intake reduced the prevalence of arsenic-mediated hypertension by lowering serum arsenic levels. Additionally, our cell-free assay revealed the adsorption-modifying effect of milk on arsenic components in a popular fish meat. An in vivo assay confirmed that milk intake significantly decreased total serum arsenic levels in mice. CONCLUSIONS: Our multidisciplinary approach, combining epidemiological, chemical and animal studies, suggests that milk consumption has a beneficial effect in reducing the prevalence of arsenic-induced hypertension by decreasing arsenic absorption. Considering the global trend for increased consumption of fish meat with high levels of total arsenic, milk may be globally useful for reducing the risk of arsenic-mediated hypertension.

Harmful health effects of exposure to low-frequency noise (LFN) defined as noise with frequencies at ≤100 Hz on the circulatory system have been a concern. However, there has been no study on the effects of exposure to LFN on the circulatory system with consideration of its frequencies and decibels. In this study, the effects of short-term exposure to broad-band LFNs and their pure-tone components (pure-tone LFNs) on cutaneous blood flow in the extremities including the hands were investigated. In our fieldwork study, we first sampled some kinds of common broad-band LFNs. Our human study then showed that broad-band LFN with a narrower frequency range more strongly increased cutaneous blood flow than did broad-band LFN with a wider frequency range. Pure-tone LFNs of 70-100 Hz at ≤85 dB(Z), but not pure-tone LFNs exceeding 100 Hz, further increased levels of cutaneous blood flow. Our wavelet-transform spectrum analysis of cutaneous blood flow next revealed that the nitric oxide (NO)-dependent and -independent vascular activities of the vascular endothelium were specifically increased by exposure to pure-tone LFN. Our animal study again indicated that exposure to pure-tone LFN increased cutaneous blood flow in mice with impairments of bilateral inner ears as well as cutaneous blood flow in control mice, suggesting a limited effect of inner ear function on the LFN-mediated increase in cutaneous blood flow. The NO-dependent suppressive effect of pure-tone LFN on cutaneous blood flow was confirmed by inhibition of vascular endothelial activity through intravenous injection of an NO inhibitor in wild-type mice. Taken together, the results of this study demonstrated that the vascular endothelium is a target tissue of LFN and that NO is an effector of the LFN-mediated increase in cutaneous blood flow. Since improvement of peripheral circulation could generally promote human health, short-term exposure to LFN may be beneficial for health.

Well water could be a stable source of drinking water. Recently, the use of well water as drinking water has been encouraged in developing countries. However, many kinds of disorders caused by toxic elements in well drinking water have been reported. It is our urgent task to resolve the global issue of element-originating diseases. In this review article, our multidisciplinary approaches focusing on oncogenic toxicities and disturbances of sensory organs (skin and ear) induced by arsenic and barium are introduced. First, our environmental monitoring in developing countries in Asia showed elevated concentrations of arsenic and barium in well drinking water. Then our experimental studies in mice and our epidemiological studies in humans showed arsenic-mediated increased risks of hyperpigmented skin and hearing loss with partial elucidation of their mechanisms. Our experimental studies using cultured cells with focus on the expression and activity levels of intracellular signal transduction molecules such as c-SRC, c-RET, and oncogenic RET showed risks for malignant transformation and/or progression arose from arsenic and barium. Finally, our original hydrotalcite-like compound was proposed as a novel remediation system to effectively remove arsenic and barium from well drinking water. Hopefully, comprehensive studies consisting of (1) environmental monitoring, (2) health risk assessments, and (3) remediation will be expanded in the field of environmental health to prevent various disorders caused by environmental factors including toxic elements in drinking water.

Chemical leukoderma is a patchy hypopigmentation in the skin. Phenol derivatives such as raspberry ketone have been reported to cause the development of occupationally induced leukoderma. Recently, 2% (w/w) rhododenol, a reduced form of raspberry ketone used in a skin-lightning agent, also caused the development of leukoderma in >16,000 users, about 2% of all users, in Asian countries including Japan. However, a method for assessing the risk of leukoderma caused by 2% rhododenol has not been established despite the fact that the development of leukoderma caused by 30% rhododenol was previously shown in animal experiments. Establishment of a novel technique for risk assessment of leukoderma in humans caused by external treatment with chemicals is needed to prevent a possible future chemical disaster. This study demonstrated that external treatment with 2% rhododenol and the same concentration of raspberry ketone caused the development of leukoderma in murine tail skin without exception with significant decreases in the amount of melanin and number of melanocytes in the epidermis. Thus, a novel in vivo technique that can assess the risk of leukoderma caused by 2% rhododenol was developed. The unique technique using tail skin has the potential to prevent chemical leukoderma in the future.