{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:15:24Z","timestamp":1791098124176,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science & Technology, Govt of India","award":["SR\/SO\/HS-41\/2002"],"award-info":[{"award-number":["SR\/SO\/HS-41\/2002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Hepatology"],"published-print":{"date-parts":[[2022,9,8]]},"abstract":"<jats:p>Background and Aims. The cellular mechanism of liver injury related to arsenic toxicity is ill defined. It is thought that oxidative stress and mitochondrial dysfunction may play some role in arsenic-induced liver damage. In this study, we evaluated subcellular events within the primary cultured mouse hepatocytes when exposed to inorganic arsenic. Methods. Primary cultured mouse hepatocytes were treated with 10\u2009\u03bcM arsenic for different time periods. Reactive oxygen species (ROS) formation, functional changes of the lysosome and mitochondria, and mode of hepatocytes death were studied by laser confocal microscopy, fluorescence spectroscopy, and flow cytometry. Expression of proapoptotic member of the BCL-2 family of genes BAX and antiapoptotic BCL-2 mRNA expression were studied by real-time PCR. Cytochrome c expression was studied by Western blotting. Results. Fluorescence spectroscopy as well as flow cytometric analysis revealed that arsenic-induced formation of ROS was time dependent. Confocal microscopy showed initiation of ROS formation from periphery of the hepatocytes at 30\u2009min of arsenic exposure that progressed to central part of the hepatocytes at 3\u2009h of arsenic exposure. The ROS formation was found to be NADPH oxidase (NOX) dependent. This low level of intracellular ROS induced lysosomal membrane permeabilization (LMP) and subsequently released cathepsin B to the cytosol. The LMP further increased intracellular ROS which in turn triggered induction of mitochondrial permeability transition (MPT). Pretreatment of hepatocytes with LMP inhibitor bafilomycin A (BafA) significantly decreased, and LMP inducer chloroquine (ChQ) significantly increased the production of ROS suggesting that LMP preceded enhanced ROS generation in response to arsenic. MPT was accompanied with increase in BAX\u2009:\u2009BCL2 mRNA ratio resulting in upregulation of caspase 3 and increased hepatocyte apoptosis. Conclusion. Although arsenic-related oxidative liver injury is well established, neither the site of origin of ROS nor the early sequence of events in arsenic toxicity due to ROS is known. We believe that our study provides evidences elucidating the early sequence of events that culminates in the death of the mouse hepatocytes during arsenic exposure.<\/jats:p>","DOI":"10.1155\/2022\/1546297","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T23:05:18Z","timestamp":1662678318000},"page":"1-12","source":"Crossref","is-referenced-by-count":13,"title":["Arsenic-Induced Injury of Mouse Hepatocytes through Lysosome and Mitochondria: An In Vitro Study"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6152-1916","authenticated-orcid":true,"given":"Amal","family":"Santra","sequence":"first","affiliation":[{"name":"JCM Centre for Liver Research and Innovations, Kolkata, India"},{"name":"Liver Foundation, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasree","family":"Bishnu","sequence":"additional","affiliation":[{"name":"JCM Centre for Liver Research and Innovations, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Santra","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhadip","family":"Ghatak","sequence":"additional","affiliation":[{"name":"Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6483-5985","authenticated-orcid":true,"given":"Partha Sarathi","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"JCM Centre for Liver Research and Innovations, Kolkata, India"},{"name":"Liver Foundation, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-5067","authenticated-orcid":true,"given":"Gopal Krishna","family":"Dhali","sequence":"additional","affiliation":[{"name":"Liver Foundation, Kolkata, West Bengal, India"},{"name":"Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9198-4436","authenticated-orcid":true,"given":"Abhijit","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"JCM Centre for Liver Research and Innovations, Kolkata, India"},{"name":"Liver Foundation, Kolkata, West Bengal, India"},{"name":"Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gsf.2020.08.015"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-011-5864-0_10"},{"key":"3","first-page":"559","article-title":"Source, distribution, toxicity and remediation of arsenic in the environment - a review","volume":"11","author":"Y. 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