Ammonium tetrathiomolybdate(VI) is an inorganic compound composed of ammonium cations and tetrathiomolybdate(VI) anions. Ammonium tetrathiomolybdate(VI) is commonly used in metabolic research of cardiovascular and cerebrovascular diseases and as a chelating agent for heavy metal detoxification[1]. The chemical formula of Ammonium tetrathiomolybdate(VI) is (NH₄)₂MoS₄. Ammonium tetrathiomolybdate(VI) serves as a source of molybdenum in biological systems. Ammonium tetrathiomolybdate(VI) is particularly valuable in the study of molybdenum-dependent enzymes such as sulfite oxidase and xanthine oxidase[2]. The thiolate ligands in this compound enable Ammonium tetrathiomolybdate(VI) to act as a chelator, binding to heavy metals like copper and iron.The neuroprotective effects of Ammonium tetrathiomolybdate (VI) are receiving extensive attention in cerebral ischemia research[3]. Additionally, Ammonium tetrathiomolybdate(VI) copper chelation complexes exhibit antibacterial properties[4].
In vitro, AC16 cardiomyocytes were treated with Ammonium tetrathiomolybdate(VI) (20μM). Pre-treatment with Ammonium tetrathiomolybdate(VI) significantly increased cell viability, indicating Ammonium tetrathiomolybdate(VI) protective effect against copper-induced cytotoxicity[5]. In HeLa cells, treatment with Ammonium tetrathiomolybdate(VI) (20μM) failed to affect the increase in LC3-II levels induced by ML-SA5 (1μM) and could not reverse the autophagy-inhibiting effect of ML-SA5[6].
In vivo, a rat model of focal cerebral ischemia-reperfusion (tMCAO, ischemia for 90 minutes) was established. Ammonium tetrathiomolybdate(VI) (10mg/kg) was administered intravenously immediately before reperfusion, followed by continuous intravenous infusion at 10mg/kg/h for 60 minutes. This treatment improved the motor coordination and spontaneous movement duration of tMCAO mice and reduced the infarct area[7]. In a model of endometriosis induced by autologous uterine tissue transplantation in TNFR1⁻/⁻ female C57BL/6 mice, oral administration of Ammonium tetrathiomolybdate(VI) (0.3mg) for 1 month resulted in the chelation of copper ions, downregulation of estradiol levels and angiogenesis-related genes, inhibition of cell proliferation, and induction of oxidative stress. These effects collectively slowed the progression of endometriosis in TNFR1⁻/⁻ mice[8].
References:
[1] Zhang M, Qiu H, Mao L, et al. Ammonium tetrathiomolybdate triggers autophagy-dependent NRF2 activation in vascular endothelial cells. Cell Death Dis. 2022 Aug 25;13(8):733.
[2] Langlois DK, Querubin JR, Schall WD, et al. Ammonium tetrathiomolybdate treatment of copper-associated hepatopathy in dogs. J Vet Intern Med. 2019 May;33(3):1336-1343.
[3] Mendonça BP, Cardoso JDS, Michels M, et al. Neuroprotective effects of ammonium tetrathiomolybdate, a slow-release sulfide donor, in a rodent model of regional stroke. Intensive Care Med Exp. 2020 Apr 9;8(1):13.
[4] Zhang L, Tsai IC, Ni Z, et al. Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis. Int J Mol Sci. 2024 May 28;25(11):5890.
[5] Huo S, Wang Q, Shi W, et al. ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury. Int J Mol Sci. 2023 Jan 14;24(2):1667.
[6] Qi J, Xing Y, Liu Y, et al. MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc influx. Autophagy. 2021 Dec;17(12):4401-4422.
[7] Dyson A, Dal-Pizzol F, Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models. PLoS Med. 2017 Jul 5;14(7):e1002310.
[8] Conforti RA, Delsouc MB, Zabala AS, et al. The copper chelator ammonium tetrathiomolybdate inhibits the progression of experimental endometriosis in TNFR1-deficient mice. Sci Rep. 2023 Jun 26;13(1):10354.
Ammonium tetrathiomolybdate(VI)是一种由铵阳离子和四硫代钼酸根(VI)阴离子组成的无机化合物，常用于心脑血管等疾病的代谢研究及作为重金属解毒的螯合剂[1]。Ammonium tetrathiomolybdate(VI)的化学式为(NH₄)₂MoS₄，作为生物系统中钼的来源，在研究亚硫酸盐氧化酶和黄嘌呤氧化酶等钼依赖酶时具有重要价值[2]。Ammonium tetrathiomolybdate(VI)的硫醇盐配体使其能够作为螯合剂，与铜、铁等重金属结合。在脑缺血研究中，Ammonium tetrathiomolybdate(VI)的神经保护作用正受到广泛关注[3]，同时Ammonium tetrathiomolybdate与铜的螯合化合物具有杀菌作用[4]。
在体外，Ammonium tetrathiomolybdate(VI) (20μM)处理AC16心肌细胞，Ammonium tetrathiomolybdate(VI)的预处理能够显著提高细胞的存活率，且Ammonium tetrathiomolybdate(VI)对铜诱导的细胞毒性具有保护作用[5]。Ammonium tetrathiomolybdate(VI) (20μM)处理HeLa细胞，Ammonium tetrathiomolybdate(VI)未能影响由ML-SA5（1μM）诱导的LC3-II水平增加，且无法逆转ML-SA5的自噬抑制作用[6]。
在体内，建立大鼠局灶性脑缺血再灌注模型（tMCAO，缺血90分钟），在再灌注前立即通过静脉注射 Ammonium tetrathiomolybdate(VI)（10mg/kg），随后持续静脉输注10mg/kg/h维持60分钟，Ammonium tetrathiomolybdate(VI)可提升tMCAO小鼠的运动协调能力和自发运动活动时间，并降低脑梗死面积[7]。取自体子宫组织移植诱导子宫内膜异位症模型的TNFR1⁻/⁻雌性C57BL/6小鼠口服Ammonium tetrathiomolybdate(VI)（0.3mg），连续1个月。Ammonium tetrathiomolybdate(VI)可通过螯合铜离子，下调雌二醇水平及血管生成相关基因，抑制细胞增殖并诱导氧化应激，从而减缓TNFR1⁻/⁻小鼠子宫内膜异位症的进展[8]。