Methylthiouracil: Anti-inflammatory Properties and Determination by Electrochemical Sensor

General Description

Methylthiouracil, primarily known as an antithyroid drug, exhibits significant anti-inflammatory properties, particularly in managing vascular inflammation. It inhibits PolyP-mediated inflammatory responses, reduces vascular barrier permeability, and suppresses key inflammatory mediators like NF-κB, TNF-α, and IL-6. This repositioning of Methylthiouracil suggests its potential in treating systemic inflammatory diseases. Additionally, advancements in electrochemical sensors for detecting Methylthiouracil have shown high reliability, with a detection limit of 0.13 µg L−1 and recovery rates between 85% and 95%, indicating precision and sustainability in meat analysis. Overall, Methylthiouracil demonstrates promise as both an anti-inflammatory agent and a detectable compound in food safety.

Figure 1. Methylthiouracil

Anti-inflammatory Properties

Introduction to Methylthiouracil and its Anti-inflammatory Properties

Methylthiouracil is primarily known as an antithyroid drug, but recent studies have unveiled its significant anti-inflammatory properties. Traditionally, Methylthiouracil has been used to treat hyperthyroidism, but the repositioning of this drug has led to new insights regarding its potential therapeutic applications in inflammatory diseases. One of its notable mechanisms involves the suppression of polyphosphate (PolyP)-mediated inflammatory responses. PolyP, released during various pathological conditions, triggers pro-inflammatory activities in endothelial cells, particularly in human umbilical vein endothelial cells (HUVECs). In this context, Methylthiouracil’s ability to modulate these responses opens avenues for its use in managing systemic inflammatory conditions. ¹

Mechanism of Action in Vascular Inflammation  

The anti-inflammatory effects of methylthiouracil are particularly evident when examining its action on vascular inflammation. Methylthiouracil effectively mitigates PolyP-induced vascular barrier permeability, which is crucial during septic conditions. Research has shown that Methylthiouracil diminishes the up-regulation of inflammatory biomarkers and inhibits the adhesion and migration of leukocytes, which are key processes in inflammation. Furthermore, Methylthiouracil downregulates the activation of critical inflammatory mediators, such as nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). This multifaceted approach positions Methylthiouracil as a potent agent in counteracting the severe inflammatory responses typically seen in conditions like sepsis or septic shock. ¹

Therapeutic Implications

The implications of methylthiouracil in treating inflammatory diseases are significant. By demonstrating protective effects against PolyP-mediated lethal outcomes and reducing septic biomarkers, Methylthiouracil shows considerable promise in the realm of drug repositioning for inflammatory treatment protocols. The capacity of Methylthiouracil to not only inhibit inflammatory pathways but also enhance endothelial cell survival indicates its potential as a therapeutic agent. As researchers continue to investigate the broader applications of Methylthiouracil, its utility in managing various systemic inflammatory diseases stands out, highlighting the importance of exploring existing medications for new roles in medical therapy. This demonstrates the valuable intersection of pharmacology and molecular biology in discovering effective treatments for complex inflammatory diseases. ¹

Determination by Electrochemical Sensor

Electrochemical Sensor Development for Methylthiouracil

The determination of Methylthiouracil has seen significant advancements through the use of electrochemical sensors, specifically voltammetric and amperometric techniques. These miniaturized sensors have been optimized for the analysis of Methylthiouracil in various meat samples, including beef liver and foie. A systematic multivariate approach was employed to optimize the extraction and detection processes. The sensors operate effectively at a working potential of 1.55 V (vs Ag pseudo-reference electrode), providing a linear response within the concentration range of 0 to 20 µg L−1 for Methylthiouracil. With a remarkably low empirical limit of detection of 0.13 µg L−1, these methods surpass legal requirements.

Reliability and Sustainability of Methylthiouracil Measurements

The electrochemical methods developed for the determination of Methylthiouracil have demonstrated great reliability and accuracy. When applied to Methylthiouracil-spiked meat samples, recovery rates varied between 85% and 95%, with coefficients of variation below 30%, indicating high precision in measurement. Comparisons with traditional analytical techniques, such as UV-Vis spectrophotometry, reveal that the results from electrochemical sensors for Methylthiouracil concentration align closely with those obtained from these conventional methods. Additionally, the sustainability aspect of the electrochemical sensor approach has been assessed using the Analytical Eco-Scale, underscoring an eco-friendly dimension to the analytical process. Overall, the electrochemical determination of Methylthiouracil represents a significant leap forward in meat analysis with its high performance and sustainability.

Reference

1. Min G, Ku SK, Jeong S, Baek MC, Bae JS. Suppressive effects of methylthiouracil on polyphosphate-mediated vascular inflammatory responses. J Cell Mol Med. 2016 Dec; 20(12): 2333-2340.

2. Marco A, Canals A, Morallón E, Aguirre Má. Electrochemical Sensor for the Determination of Methylthiouracil in Meat Samples. Sensors (Basel). 2022 Nov 15; 22(22): 8842.

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