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The purpose of the present work was to obtain a general view about the acute effects of arsenic trioxide on liver metabolism using the isolated perfused rat liver, a system that preserves microcirculation and cell polarity. Hepatic lactate and alanine gluconeogenesis were inhibited by arsenic trioxide with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 21.7 and 21.4\u00a0\u00b5M, respectively. Oxygen uptake was inhibited only at concentrations above the IC\n                    <jats:sub>50<\/jats:sub>\n                    value for gluconeogenesis inhibition. In addition to the carbon fluxes derived from alanine metabolism, arsenic trioxide also inhibited nitrogen detoxification (urea production) with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 47.9\u00a0\u00b5M. Glycolysis from endogenous glycogen was stimulated at concentrations of up to 25\u00a0\u00b5M. Fructose metabolism was also affected: transformation into glucose was inhibited and fructolysis was stimulated. Glycerol metabolism was not modified. The ATP levels were not significantly diminished, but arsenic trioxide inhibited pyruvate carboxylase and phosphoenolpyruvate carboxykinase, phenomena that seem to be the main cause for gluconeogenesis inhibition. The acute effects of arsenic trioxide described herein are likely to contribute significantly to the general toxicity of the compound especially when combined with the reported long-term induction of exacerbated reactive oxygen species (ROS) production. When using the compound as a therapeutic agent, extreme care must be taken to avoid even mild overdosing as harmful and therapeutic levels for acute promyelocytic leukemia treatment are in fact relatively close to each other.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05458-8","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T03:05:53Z","timestamp":1779505553000},"page":"17469-17483","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-term actions of arsenic trioxide on metabolic fluxes in the isolated perfused rat liver"],"prefix":"10.1007","volume":"399","author":[{"given":"Nairana Mithieli","family":"de Queiroz Eskuarek Melo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosane Marina","family":"Peralta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"Bracht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelar","family":"Bracht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"5458_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2147\/OTT.S38227","volume":"6","author":"S Alarifi","year":"2013","unstructured":"Alarifi S, Ali D, Alkatahni S, Siddiqui MA, Ali BA (2013) Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells. 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