Methimazole is an antithyroid agent and has anti-inflammatory activity, with an IC50 value of 10µM for inhibiting prostaglandin H synthase [1]. Methimazole prevents oxidation and tyrosine coupling of iodide absorbed into the thyroid gland, which in turn inhibits thyroxine synthesis [2]. Methimazole has been widely used to regulate the mitochondrial function of liver cells and to reduce the level of glutathione[3].
In vitro, Methimazole treatment (40mM) for 48 hours significantly inhibited the viability of PANC-1 cells and increased the production of reactive oxygen species (ROS)[4]. Treatment with 2mM Methimazole for 24 hours significantly caused S-phase arrest in FRTL5 thyroid cells[5]. Treatment with 10mM Methimazole for 3 days significantly increased the sensitivity of thyroid epithelial cells (TECs) to H2O2, promoted cell apoptosis, and caused irregular shapes of the cell nuclei[6].
In vivo, Methimazole treatment via a single intraperitoneal injection at a dose of 400mg/kg for 5 hours significantly induced a decrease in the liver mitochondrial membrane potential of the mice, and reduced the contents of ATP and glutathione in the liver mitochondria[7]. Administering 60mg/kg of Methimazole orally daily for 4 weeks resulted in a decrease in rectal temperature and body weight in Wistar rats and caused cell damage in the liver, kidneys, spleen, and heart[8].
References:
[1] Lagorce J F, Moulard T, Rousseau A, et al. Anti-inflammatory action of methimazole[J]. Pharmacology, 1997, 55(4): 173-178.
[2] Liu Y, Li Q, Xu Y, et al. Comparison of the safety between propylthiouracil and methimazole with hyperthyroidism in pregnancy: A systematic review and meta-analysis[J]. PLoS One, 2023, 18(5): e0286097.
[3] Heidari R, Babaei H, Eghbal M. Mechanisms of methimazole cytotoxicity in isolated rat hepatocytes[J]. Drug and chemical toxicology, 2013, 36(4): 403-411.
[4] Yazıcı Ö, Kara M, Boran T, et al. The role of endoplasmic reticulum stress in cell injury induced by methimazole on pancreatic cells[J]. Advanced pharmaceutical bulletin, 2022, 13(1): 196.
[5] Smerdely P, Pitsiavas V, Boyages S C. Methimazole inhibits FRTL5 thyroid cell proliferation by inducing S-phase arrest of the cell cycle[J]. Endocrinology, 1993, 133(5): 2403-2406.
[6] Landex N L, Thomsen J, Kayser L. Methimazole increases H2O2 toxicity in human thyroid epithelial cells[J]. Acta histochemica, 2006, 108(6): 431-439.
[7] Niknahad H, Jamshidzadeh A, Heidari R, et al. Paradoxical effect of methimazole on liver mitochondria: in vitro and in vivo[J]. Toxicology letters, 2016, 259: 108-115.
[8] Cano-Europa E, Blas-Valdivia V, Franco-Colin M, et al. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney[J]. Acta histochemica, 2011, 113(1): 1-5.
Methimazole是一种抗甲状腺药物，具有抗炎活性，抑制prostaglandin H synthase的IC50值为10µM[1]。Methimazole可防止被甲状腺摄取的碘发生氧化和酪氨酸偶联，从而抑制甲状腺素的合成[2]。Methimazole已被广泛用于调节肝细胞的线粒体功能并降低谷胱甘肽水平[3]。
在体外，40mM的Methimazole处理PANC-1细胞48小时，显著抑制了细胞活力，并增加了活性氧(ROS)的产生[4]。2mM的Methimazole处理FRTL5甲状腺细胞24小时，显著引起了S期阻滞[5]。10mM的Methimazole处理3天，显著增加了甲状腺上皮细胞(TECs)对H2O2的敏感性，促进了细胞凋亡，并导致了细胞核形态不规则[6]。
在体内，单次腹腔注射400mg/kg剂量的Methimazole，处理5小时，显著诱导了小鼠肝脏线粒体膜电位的下降，并降低了肝脏线粒体中ATP和谷胱甘肽的含量[7]。每日口服60mg/kg的Methimazole，连续4周，导致Wistar大鼠的直肠温度和体重下降，并引起肝脏、肾脏、脾脏和心脏的细胞损伤[8]。