| Title: | Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies |
| Journal: | Allergy |
| Published: | 10 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37129453/ |
| DOI: | https://doi.org/10.1111/all.15758 |
| URL: | https://doi.org/10.22541/au.167358975.59115690/v1 |
Publication 11432
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Abstract
BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated.</p>
METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen.</p>
RESULTS: Hair arsenic (μg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum β-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of β-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (β = -0.98, p = 0.04).</p>
CONCLUSION: Arsenic exposure is associated with pruritus, and β-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.</p>
13 Authors
- Xiaoyan Huang
- Yi Xiao
- Danrong Jing
- Yuzhou Huang
- Songchun Yang
- Zhijun Huang
- Guoping Yang
- Yanying Duan
- Meian He
- Juan Su
- Mingliang Chen
- Xiang Chen
- Minxue Shen
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