{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:16:19Z","timestamp":1771236979110,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\u03b1\u2010amanitin (\u03b1\u2010AMA), the primary lethal toxin of amanita, primarily targets the liver with a high toxicity and a low lethal dose. As the precise mechanism of intoxication is unclear, and specific antidotes are lacking, \u03b1\u2010AMA\u2010induced liver injury has a high mortality rate. As a selective PPAR\u2010\u03b3 agonist, Rosiglitazone (RSG) alleviates liver injury by upregulating the PPAR\u2010\u03b3\/Nrf2 signaling pathway, thereby enhancing antioxidant effects, mitigating inflammation, and reducing apoptosis. This study investigated the protective role and mechanism of action of RSG in \u03b1\u2010AMA\u2010induced acute liver injury in ICR mice. We established an experimental model and examined hepatic injury markers, focusing on PPAR\u2010\u03b3\/Nrf2 pathway activation. Overall, \u03b1\u2010AMA intoxication led to dose\u2010dependent increases in serum ALT\/AST levels, accompanied by hepatocellular necrosis. This was associated with the onset of oxidative stress, characterized by the accumulation of malondialdehyde (MDA), excessive ROS production, and reduced activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Furthermore, we observed the upregulation of pro\u2010inflammatory mediators (TNF\u2010\u03b1, IL\u20106, and IL\u20108), suppression of the PPAR\u2010\u03b3\/Nrf2 cytoprotective axis, and hepatocyte apoptosis induced via activation of the P53\/caspase\u20103 pathway, ultimately resulting in murine mortality. RSG treatment alleviated oxidative stress and the inflammatory response, reduced hepatocellular necrosis and apoptosis, and improved survival rates in \u03b1\u2010AMA\u2010intoxicated mice by upregulating the PPAR\u2010\u03b3\/Nrf2 signaling pathway in hepatocytes. Early RSG intervention can thereby effectively mitigate \u03b1\u2010AMA\u2010induced acute liver injury by upregulating the PPAR\u2010\u03b3\/Nrf2 signaling pathway. Future studies should focus on exploring the clinical potential of RSG as a therapeutic agent for amanita mushroom poisoning.<\/jats:p>","DOI":"10.1002\/jbt.70701","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:51:45Z","timestamp":1768978305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective Effect and Mechanism of Rosiglitazone in \u03b1\u2010amanitin\u2010induced Hepatotoxicity Via Activation of PPAR\u2010\u03b3\/Nrf2 Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Fuping","family":"Lai","sequence":"first","affiliation":[{"name":"Emergency Department The Affiliated Hospital of Zunyi Medical University Zunyi Guizhou China"},{"name":"Emergency Department Longyan First Affiliated Hospital of Fujian Medical University Longyan Fujian 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