{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:15:43Z","timestamp":1785363343058,"version":"3.55.0"},"reference-count":157,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>TRPM2 channels admit Ca2+ and Na+ across the plasma membrane and release Ca2+ and Zn2+ from lysosomes. Channel activation is initiated by reactive oxygen species (ROS), leading to a subsequent increase in ADP-ribose and the binding of ADP-ribose to an allosteric site in the cytosolic NUDT9 homology domain. In many animal cell types, Ca2+ entry via TRPM2 channels mediates ROS-initiated cell injury and death. The aim of this review is to summarise the current knowledge of the roles of TRPM2 and Ca2+ in the initiation and progression of chronic liver diseases and acute liver injury. Studies to date provide evidence that TRPM2-mediated Ca2+ entry contributes to drug-induced liver toxicity, ischemia\u2013reperfusion injury, and the progression of non-alcoholic fatty liver disease to cirrhosis, fibrosis, and hepatocellular carcinoma. Of particular current interest are the steps involved in the activation of TRPM2 in hepatocytes following an increase in ROS, the downstream pathways activated by the resultant increase in intracellular Ca2+, and the chronology of these events. An apparent contradiction exists between these roles of TRPM2 and the role identified for ROS-activated TRPM2 in heart muscle and in some other cell types in promoting Ca2+-activated mitochondrial ATP synthesis and cell survival. Inhibition of TRPM2 by curcumin and other \u201cnatural\u201d compounds offers an attractive strategy for inhibiting ROS-induced liver cell injury. In conclusion, while it has been established that ROS-initiated activation of TRPM2 contributes to both acute and chronic liver injury, considerable further research is needed to elucidate the mechanisms involved, and the conditions under which pharmacological inhibition of TRPM2 can be an effective clinical strategy to reduce ROS-initiated liver injury.<\/jats:p>","DOI":"10.3390\/antiox10081243","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T02:16:07Z","timestamp":1628043367000},"page":"1243","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-3500","authenticated-orcid":false,"given":"Eunus S.","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, College of Medicine and Public Health, Flinders University G. P. O. Box 2100, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigori Y.","family":"Rychkov","sequence":"additional","affiliation":[{"name":"School of Medicine, The University of Adelaide, and South Australian Health and Medical Research Institute, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7472-4250","authenticated-orcid":false,"given":"Greg J.","family":"Barritt","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, College of Medicine and Public Health, Flinders University G. P. O. Box 2100, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ali, E.S., Rychkov, G.Y., and Barritt, G.J. (2020). 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