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.