Ebselen a Seleno-organic Molecule Inhibits Alteration in the Biological Responses in Hypoxic Human Alveolar Lung Epithelial Cells
Neetu Kushwah
Neurobiology Division, Defence Institute of Physiology & Allied Sciences, DRDO, Lucknow Road, Timarpur, Delhi-110054, India.
Amit Prabhakar
Neurobiology Division, Defence Institute of Physiology & Allied Sciences, DRDO, Lucknow Road, Timarpur, Delhi-110054, India.
Dipti Prasad
Neurobiology Division, Defence Institute of Physiology & Allied Sciences, DRDO, Lucknow Road, Timarpur, Delhi-110054, India.
K. Ravi
Department of Physiology, VP Chest Institute, University of Delhi, Delhi-11008, India.
Shashi Bala Singh
Neurobiology Division, Defence Institute of Physiology & Allied Sciences, DRDO, Lucknow Road, Timarpur, Delhi-110054, India.
Nilofar Khan *
Neurobiology Division, Defence Institute of Physiology & Allied Sciences, DRDO, Lucknow Road, Timarpur, Delhi-110054, India.
*Author to whom correspondence should be addressed.
Abstract
Ebselen is a lipid-soluble seleno-organic compound whose benefits have been shown in a variety of diseases and in experimental studies including anti-inflammation, anti-proliferation, anti-angiogenesis, anti carcinogenesis and anti-oxidation properties. This study aimed to evaluate the effect of ebselen against hypoxia-induced biological responses in human alveolar epithelial cells (A549 cells). Hypoxia treatment increased the generation of reactive oxygen species, proinflammatory cytokines/chemokines, cell death and proliferation in A549 cells in a time-dependent manner. Notably, Ebselen treatment significantly reduced the production of reactive oxygen species and levels of biochemical markers for lipid peroxidation. Ebselen treatment increased the antioxidant enzyme superoxide dismutase activity as well. This seleno-organic compound also reduced the production of proinflammatory chemokines IL-8 and proinflammatory cytokine TNF-α. It is worth noticing that, Ebselen enhanced the viability as well as proliferation of hypoxic A549 cells. Collectively, these data demonstrate that the Ebselen attenuates the alterations in biological responses in hypoxic human alveolar epithelial cells. Our results further suggest that that ebselen could be used as a potential chemopreventive compound to restore the normal biological response in hypoxic cells and thus inhibiting the progression of the lung carcinoma.
Keywords: Hypoxia, oxidative stress, ebselen, inflammation, alveolar lung epithelial cells, A549 cells, reactive oxygen species, lung carcinoma