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Abstract
Tyrosine phenol-lyase (TPL), which is expressed in intestinal bacteria, catalyzes the formation of phenol from the substrate L-Tyr. Bacterial metabolite phenol and the sulfate conjugate (phenyl sulfate) are known as a type of uremic toxins, some of which exert cytotoxicity. Therefore, pathologically elevated phenol and phenyl sulfate levels are strongly implicated in the etiology and outcome of uremia. In this study, we explored the inhibitory effects of dietary polyphenols on TPL-catalyzed phenol production using a TPL activity assay. Quercetin, one of the most popular polyphenols, exhibited the strongest inhibitory activity (Ki = 19.9 µM). Quercetin competitively inhibited TPL, and its activity was stronger than that of a known TPL inhibitor (Tyr analog; 2-aza-Tyr, Ki = 42.0 µM). Additionally, quercetin significantly inhibited phenol production in TPL-expressing bacterial cultures (Morganella morganii and Citrobacter koseri) and Tyr-rich (5%) diet-fed C57BL/6J mouse feces. Our findings suggest that quercetin is the most promising polyphenol for reducing phenol levels. Because quercetin has a low gastrointestinal absorption rate, TPL inhibition in the intestinal tract by quercetin may be an effective strategy for treating uremia.

"This Skin Notation Profile presents (1) a brief summary of technical data associated with skin contact with Phenol and (2) the rationale behind the hazard-specific skin notation (SK) assignment for Phenol. The SK assignment is based on the scientific rationale and logic outlined in the Current Intelligence Bulletin (CIB) 61: A Strategy for Assigning New NIOSH Skin Notations [NIOSH 2009]. The summarized information and health hazard assessment are limited to an evaluation of the potential health effects of dermal exposure to Phenol. A literature search was conducted through July 2010 to identify information on Phenol, including but not limited to data relating to its toxicokinetics, acute toxicity, repeated-dose systemic toxicity, carcinogenicity biological system/function-specific effects (including reproductive and developmental effects and immunotoxicity), irritation, and sensitization. Information was considered from studies of humans, animals, or appropriate modeling systems that are relevant to assessing the effects of dermal exposure to Phenol. Phenol is potentially capable of causing both systemic toxicity and direct adverse effects on the skin following dermal exposure. A critical review of available data indicates that contact of a significant area of skin with subjectively low concentrations of phenol (5-6%) may be extremely hazardous and life-threatening [ATSDR 2008]. Undiluted phenol or solutions containing more than 3% phenol are capable of causing skin corrosion, whereas diluted solutions (1 to 3% phenol) are irritating to the skin [European Parliament 2008]. NIOSH has designated phenol with the following SK assignment: SK: SYS (FATAL)-DIR (COR). Table 1 provides an overview of the critical effects and data considered in the development of this SK assignment. The following section provides additional detail about the potential health hazards of skin contact with phenol and the rationale behind the SK assignment." - NIOSHTIC-2 ; Foreword -- Abbreviations -- Glossary -- Acknowledgments -- 1. Introduction -- 1.1. General Substance Information -- 1.2. Purpose -- 1.3. Overview of SK Assignment for Phenol -- 2. Systemic Toxicity from Skin Exposure (SK: SYS) -- 3. Direct Effects on Skin (SK: DIR) -- 4 Immune-mediated Responses (SK: SEN) -- 5. Summary -- References -- Appendix: Calculation of the SI Ratio for Phenol ; "This document was developed by the Education and Information Division, Paul Schulte, Ph.D., Director. G. Scott Dotson, Ph.D. was the project officer for this document. Other NIOSH personnel, in particular Eric Esswein, M.Sc., Charles L. Geraci, Ph.D., Thomas J. Lentz, Ph.D., Richard Niemeier, Ph.D., and Loren Tapp, M.D., contributed to its development by providing technical reviews and comments. The basis for this document was a report contracted by NIOSH and prepared by Bernard Gadagbui, Ph.D., and Andrew Maier, Ph.D. (Toxicology Excellence for Risk Assessment [TERA])." -- p. ix ; "April 2011." ; Includes bibliographical references (p. 8-9). ; Also available via the World Wide Web as Acrobat .pdf file (651.89 KB, 26 p.).