Ebselen is a selenoorganic compound with glutathione peroxidase-like activity and is an anti-inflammatory and antioxidant agent[1]. Ebselen is an inhibitor of inositol monophosphatase (IMPase) with an IC50 of 1.5μM[2]. Ebselen is a potent scavenger of hydrogen peroxide and hydroperoxides, including membrane-bound phospholipid and cholesterol ester hydroperoxides[3]. Ebselen can penetrate the blood-brain barrier and has anti-inflammatory, antioxidant and anti-cancer activities[4].
In vitro, Ebselen (0-100μM) treatment of U266 and RPMI8226 cells for 24h reduced cell viability in a concentration-dependent manner, induced cell apoptosis, increased the generation of intracellular ROS, and induced the translocation of Bax protein from the cytosol to the mitochondria[5]. Ebselen (5-10μM) treatment of V79 cells reduced hydrogen peroxide-induced DNA damage[6]. Ebselen (10-20μM) inhibited the growth of A549 lung cancer cells, Calu-6 lung cancer cells and primary normal human lung fibroblasts (HPF) cells, with IC50 values of approximately 12.5μM, 10μM and 20μM, respectively[7].
In vivo, Ebselen (10mg/kg) was intraperitoneally injected into rats with spinal cord injury (SCI), which reduced the levels of malondialdehyde (MDA) and protein carbonyl (PC) in spinal cord tissue and prevented the inhibition of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) enzyme activities in tissues induced by SCI[8].
References:
[1] Nakamura Y, Feng Q, Kumagai T, et al. Ebselen, a glutathione peroxidase mimetic seleno-organic compound, as a multifunctional antioxidant: implication for inflammation-associated carcinogenesis[J]. Journal of Biological Chemistry, 2002, 277(4): 2687-2694.
[2] Ramli F F, Cowen P J, Godlewska B R. The potential use of ebselen in treatment-resistant depression[J]. Pharmaceuticals, 2022, 15(4): 485.
[3] Santofimia-Castaño P, Izquierdo-Alvarez A, de la Casa-Resino I, et al. Ebselen alters cellular oxidative status and induces endoplasmic reticulum stress in rat hippocampal astrocytes[J]. Toxicology, 2016, 357: 74-84.
[4] Ali F, Alom S, Ali S R, et al. Ebselen: A Review on its Synthesis, Derivatives, Anticancer Efficacy and Utility in Combating SARS-COV-2[J]. Mini Reviews in Medicinal Chemistry, 2024, 24(12): 1203-1225.
[5] Zhang L, Zhou L, Du J, et al. Induction of apoptosis in human multiple myeloma cell lines by ebselen via enhancing the endogenous reactive oxygen species production[J]. BioMed Research International, 2014, 2014(1): 696107.
[6] Miorelli S T, Rosa R M, Moura D J, et al. Antioxidant and anti-mutagenic effects of ebselen in yeast and in cultured mammalian V79 cells[J]. Mutagenesis, 2008, 23(2): 93-99.
[7] Park W H. Ebselen Inhibits the Growth of Lung Cancer Cells via Cell Cycle Arrest and Cell Death Accompanied by Glutathione Depletion[J]. Molecules, 2023, 28(18): 6472.
[8] Kalayci M, Coskun O, Cagavi F, et al. Neuroprotective effects of ebselen on experimental spinal cord injury in rats[J]. Neurochemical Research, 2005, 30: 403-410.
Ebselen一种具有谷胱甘肽过氧化物酶样活性的硒代有机化合物，是一种抗炎和抗氧化剂[1]。Ebselen是肌醇单磷酸酶（IMPase）的抑制剂，IC50为1.5μM[2]。
Ebselen是过氧化氢和氢过氧化物的有效清除剂，包括膜结合的磷脂和胆固醇酯氢过氧化物[3]。Ebselen能够透过血脑屏障，具有抗炎，抗氧化和抗癌活性[4]。
在体外，Ebselen（0-100μM）处理U266、RPMI8226细胞24h，以浓度依赖性方式降低了细胞活力，诱导了细胞凋亡，增加了细胞内ROS的生成，诱导了Bax蛋白从胞质溶胶转位到线粒体[5]。Ebselen（5-10μM）处理V79细胞，降低了过氧化氢诱导的DNA损伤[6]。Ebselen（10-20μM）处理A549肺癌细胞、Calu-6肺癌细胞和原代正常人肺成纤维细胞（HPF）细胞，均抑制了细胞的生长，IC50值分别约为12.5μM、10μM和20μM[7]。
在体内，Ebselen（10mg/kg）通过腹腔注射治疗脊髓损伤（SCI）大鼠，降低了脊髓组织中的丙二醛（MDA）和蛋白质羰基（PC）水平，阻止了SCI引起的组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）酶活性的抑制[8]。