Publications by authors named "Sourav Kumar Das"

3 Publications

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Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage.

Environ Pollut 2021 Mar 23;281:116969. Epub 2021 Mar 23.

Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India; Homi Bhabha National Institute, Anushakti Nagar, Mumbai, 400 094, India. Electronic address:

Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1-100 μg/ml, 24-72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity.
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http://dx.doi.org/10.1016/j.envpol.2021.116969DOI Listing
March 2021

Characterization of Thorium-Pyrazinoic acid complexation and its decorporation efficacy in human cells and blood.

Chemosphere 2021 May 4;271:129547. Epub 2021 Jan 4.

Chemical Engineering Division, Bhabha Atomic Research Centre, Mumbai, 400094, India.

Thorium (Th) exposure to the human beings is a radiochemical hazard and the chelation therapy by suitable drugs is the major prevention approach to deal with. The present studies aimed at usage of pyrazinoic acid (PCA), which is a prodrug to treat tuberculosis, for its usage as decorporating agent for thorium from human body. The present studies provide a comprehensive knowledge on the chemical interaction and biological efficacy of pyrazinoic acid (PCA) for decorporation of Thorium from the human body. The thermodynamic parameters for Th-PCA speciation are determined by both experiment and theory. The potentiometric data analysis and Electro-Spray Ionization Mass Spectrometry (ESI-MS) studies revealed the formation of ML (i = 1-4) species with the decrease in stepwise stability constants. All the species formations are endothermic reactions and are predominantly entropy-driven. Biological experiments using human erythrocytes, whole blood and normal human lung cells showed cytocompatibility and decorporation ability of PCA for Thorium. Density functional calculations have been carried out to get insights on interaction process at molecular level. The experimental results and theoretical predictions found to be in line with each other. Present findings on complexation of Th by PCA and its evaluation in human cells and blood would further motivate determination of its safety levels and decorporation efficacy in animal models.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129547DOI Listing
May 2021

Mechanistic insights on melatonin-mediated drought stress mitigation in plants.

Physiol Plant 2020 Dec 11. Epub 2020 Dec 11.

Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India.

Drought stress imposes a serious threat to crop productivity and nutritional security. Drought adaptation mechanisms involve complex regulatory network comprising of various sensory and signaling molecules. In this context, melatonin has emerged as a potential signaling molecule playing a crucial role in imparting stress tolerance in plants. Melatonin pretreatment regulates various plant physiological processes such as osmoregulation, germination, photosynthesis, senescence, primary/secondary metabolism, and hormonal cross-talk under water deficit conditions. Melatonin-mediated regulation of ascorbate-glutathione (AsA-GSH) cycle plays a crucial role to scavenge reactive oxygen species generated in the cells during drought. Here, in this review, the current knowledge on the role of melatonin to ameliorate adverse effects of drought by modulating morphological, physiological, and redox regulatory processes is discussed. The role of melatonin to improve water absorption capacity of roots by regulating aquaporin channels and hormonal cross-talk involved in drought stress mitigation are also discussed. Overall, melatonin is a versatile bio-molecule involved in growth promotion and yield enhancement under drought stress that makes it a suitable candidate for eco-friendly crop production to ensure food security.
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http://dx.doi.org/10.1111/ppl.13307DOI Listing
December 2020