**Background**
Inflammation is a complex biological response involving the release of pro-inflammatory cytokines and the activation of key signaling pathways, such as NF-κB and ERK1/2. Excessive activation of these pathways can lead to endothelial hyperpermeability and tissue damage. Simultaneously, thyroid hormones play a critical role in the maturation of the central nervous system, and their deficiency can lead to significant neurological defects. Understanding the modulation of these inflammatory and endocrine pathways is essential for developing treatments for systemic inflammation and studying neurodevelopmental disorders. In this context, we will introduce an antithyroid agent with anti-inflammatory properties – Methylthiouracil.
**Definition**
Methylthiouracil is an antithyroid agent that targets NF-κB, ERK1, ERK2, and IL-6 to suppress inflammatory responses.
**In Vitro and In Vivo Studies**
According to the Methylthiouracil description, this compound suppresses the production of TNF-α and IL-6, while inhibiting the activation of NF-κB and ERK1/2. In Methylthiouracil in vitro studies, HUVECs were treated with various concentrations of the compound (0-20 μM) for 6 h following LPS (100 ng/mL) stimulation for 4 h. The results demonstrated that Methylthiouracil inhibits LPS-mediated hyperpermeability in endothelial cells, with optimal effects observed at concentrations above 5 μM. Immunofluorescence staining of F-actin revealed that post-treatment with 10 or 20 μM of the agent inhibited the formation of LPS-induced paracellular gaps, promoting the formation of dense F-actin rings. Furthermore, cellular viability assays indicated that concentrations up to 20 μM do not affect HUVEC viability over 24 h.
Regarding Methylthiouracil In Vivo activity, the compound significantly inhibits LPS-induced peritoneal dye leakage. In mouse models, subcutaneous injections of 142 or 284 μg/kg resulted in maximum peripheral blood dye concentrations of 10 or 20 μM, respectively. In dairy cows, oral administration leads to rapid appearance in plasma, urine, and milk, with selective accumulation in the thyroid gland. Additionally, Methylthiouracil can be used to model neurological defects by inducing thyroid deficiency. Following a specific Methylthiouracil protocol in rats, subcutaneous administration of a 4% suspension in 2% sodium alginate (0.05 mL from days 0-10; 0.1 mL from days 10-20; 0.2 mL from days 20-24) resulted in decreased body weight, reduced brain weight, and diminished responsiveness to external stimuli. Histological analysis of the cerebral cortex showed a decrease in pyramidal cell volume and a reduction in the intercellular matrix between neurons. In conclusion, Methylthiouracil is a versatile agent effective for both anti-inflammatory research and the induction of thyroid-deficiency-related neurological models.
Keywords
Methylthiouracil, 56-04-2, MTU, NF-κB, TNF Receptor, Interleukin Related, ERK, Nuclear factor-κB, Nuclear factor-kappaB, Tumor Necrosis Factor Receptor, TNFR, IL, Extracellular signal regulated kinases, Inhibitor, inhibitor
References
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