{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:11:48Z","timestamp":1789567908763,"version":"build-2803163510"},"reference-count":298,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["26-15-00054"],"award-info":[{"award-number":["26-15-00054"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["26-15-00054"],"award-info":[{"award-number":["26-15-00054"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Pathological activation of oxidative metabolism is a universal catalyst for liver parenchyma destruction. While physiological pools of reactive oxygen and nitrogen species (ROS\/RNS) regulate hepatic regeneration and cellular respiration, decompensation of endogenous antioxidant systems induces cascading damage across hepatocytes, sinusoidal endothelial cells, Kupffer macrophages, and hepatic stellate cells. Current therapies against liver fibrosis, cirrhosis, and hepatocellular carcinoma remain suboptimal, necessitating the identification of novel, druggable molecular targets. Focus: This review synthesizes current evidence on ROS-driven necroinflammatory and degenerative cascades and evaluates the multi-level protective potential of the selenoprotein family. Evidence: Selenoproteins function as a highly heterogeneous network where specific members are vital for cell survival (e.g., GPX4 in preventing ferroptosis), while others exhibit stage-dependent expression throughout progression from inflammation to malignancy. Conclusions: In addition to directly scavenging free radicals, selenoproteins modulate endoplasmic reticulum stress, metabolic remodeling, and immune responses. A more complete understanding of the important role of selenoproteins in regulating liver pathological processes, particularly their antioxidant function, allows them to be considered as promising potential targets for the further development of pharmacotherapeutic strategies for the treatment of chronic liver diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091167","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological Potential of Selenoproteins in the Regulation of Oxidative Stress in Liver Diseases"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1158-5174","authenticated-orcid":false,"given":"Elena G.","family":"Varlamova","sequence":"first","affiliation":[{"name":"Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d, St. Institutskaya 3, 142290 Pushchino, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Aging, ROS, and cellular senescence: A trilogy in the progression of liver fibrosis","volume":"15","author":"Almalki","year":"2024","journal-title":"Biogerontology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1055\/s-0029-1214370","article-title":"Oxidative stress and alcoholic liver disease","volume":"29","author":"Wu","year":"2009","journal-title":"Semin. 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