Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways

被引:136
作者
Azad, Gajendra Kumar [1 ]
Tomar, Raghuvir S. [1 ]
机构
[1] Indian Inst Sci Educ & Res, Dept Biol Sci, Lab Chromatin Biol, Bhopal 462023, India
关键词
Ebselen; Organoselenium compounds; Redox biology; Antioxidant; Enzyme mimic; SELENOORGANIC COMPOUND EBSELEN; RAT HIPPOCAMPAL ASTROCYTES; FREE-RADICAL SCAVENGERS; OXIDATIVE DNA-DAMAGE; N-TERMINAL KINASE; MITOCHONDRIAL PERMEABILITY TRANSITION; PEROXIDE-INDUCED CYTOTOXICITY; ZINC-FINGER PROTEINS; MEMBRANE H+-ATPASE; INDUCED APOPTOSIS;
D O I
10.1007/s11033-014-3417-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Ebselen, an organoselenium compound, mimics glutathione peroxidase activity. It is a multifunctional compound, which catalyzes several essential reactions for the protection of cellular components from oxidative and free radical damage. Based on a number of in vitro and in vivo studies, various mechanisms are proposed to understand the biomedical actions of ebselen in health and diseases. It modulates metallo-proteins, enzymatic cofactors, gene expression, epigenetics, antioxidant defenses and immune systems. Owing to these properties, ebselen is currently under clinical trials for the prevention and treatment of various disorders such as cardiovascular diseases, arthritis, stroke, atherosclerosis, and cancer. A few ebselen-based pharmaceutical agents are under extensive investigation. As ebselen has been shown to have significant cellular toxicity, appropriate studies are needed to redesign the ebselen-based therapy for clinical trials. This review summarizes current understanding of the biochemical and molecular properties, and pharmacological applications of ebselen and future directions in this area of research.
引用
收藏
页码:4865 / 4879
页数:15
相关论文
共 178 条
[1]
ROS and RNS Signaling in Heart Disorders: Could Antioxidant Treatment Be Successful? [J].
Afanas'ev, Igor .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2011, 2011
[2]
Synchrotron radiation induced X-ray emission studies of the antioxidant mechanism of the organoselenium drug ebselen [J].
Aitken, Jade B. ;
Lay, Peter A. ;
Duong, T. T. Hong ;
Aran, Roshanak ;
Witting, Paul K. ;
Harris, Hugh H. ;
Lai, Barry ;
Vogt, Stefan ;
Giles, Gregory I. .
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 2012, 17 (04) :589-598
[3]
Ebselen inhibits p38 mitogen-activated protein kinase-mediated endothelial cell death by hydrogen peroxide [J].
Ali, N ;
Yoshizumi, M ;
Tsuchiya, K ;
Kyaw, M ;
Fujita, Y ;
Izawa, Y ;
Abe, S ;
Kanematsu, Y ;
Kagami, S ;
Tamaki, T .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 485 (1-3) :127-135
[4]
Density Functional Theory Study of the Attack of Ebselen on a Zinc-Finger Model [J].
Antony, Sonia ;
Bayse, Craig A. .
INORGANIC CHEMISTRY, 2013, 52 (24) :13803-13805
[5]
Modeling the Mechanism of the Glutathione Peroxidase Mimic Ebselen [J].
Antony, Sonia ;
Bayse, Craig A. .
INORGANIC CHEMISTRY, 2011, 50 (23) :12075-12084
[6]
Ebselen attenuates cadmium-induced testicular damage in mice [J].
Ardais, Ana P. ;
Santos, Francielli W. ;
Nogueira, Cristina W. .
JOURNAL OF APPLIED TOXICOLOGY, 2008, 28 (03) :322-328
[7]
Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods [J].
Aruoma, OI .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 523 :9-20
[8]
Multifunctional Ebselen drug functions through the activation of DNA damage response and alterations in nuclear proteins [J].
Azad, Gajendra K. ;
Balkrishna, Shah Jaimin ;
Sathish, Narayanan ;
Kumar, Sangit ;
Tomar, Raghuvir S. .
BIOCHEMICAL PHARMACOLOGY, 2012, 83 (02) :296-303
[9]
Ebselen induces reactive oxygen species (ROS)-mediated cytotoxicity in Saccha-romyces cerevisiae with inhibition of glutamate dehydrogenase being a target [J].
Azad, Gajendra Kumar ;
Singh, Vikash ;
Mandal, Papita ;
Singh, Prabhat ;
Golla, Upendarrao ;
Baranwal, Shivani ;
Chauhan, Sakshi ;
Tomar, Raghuvir S. .
FEBS OPEN BIO, 2014, 4 :77-89
[10]
BALDEW GS, 1990, CANCER RES, V50, P7031