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Here, UPLC-QqQ-MS\/MS was used to characterize L-SeMC pharmacokinetics and tissue distribution in H22 tumor-bearing mice, while untargeted metabolomics was applied to assess hepatic responses after acute administration. L-SeMC was rapidly absorbed, reaching peak plasma and tumor concentrations within 5 and 30 min, respectively. The liver and tumor showed relatively high exposure, whereas parent L-SeMC declined to near-baseline levels within 2880 min. In contrast, hepatic metabolic alterations were most pronounced at 1440 min and were mainly associated with sulfur amino acid metabolism, accompanied by increased glutathione and taurine. These findings provide a clearer characterization of the acute pharmacokinetic behavior and hepatic metabolic responses of L-SeMC and establish a pharmacokinetic basis for further investigation of its biological effects and nutritional potential.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c10372","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:01:46Z","timestamp":1791453706000},"page":"32410-32425","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Acute\nPharmacokinetics and Liver Metabolic\nResponse of\n                    <scp>L<\/scp>\n                    -Se-Methylselenocysteine in Mice Using\nUPLC-QqQ-MS\/MS and Untargeted Metabolomics"],"prefix":"10.1021","volume":"74","author":[{"given":"Hongan","family":"Li","sequence":"first","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Tang","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-1507","authenticated-orcid":true,"given":"Zeyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]},{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-7554","authenticated-orcid":true,"given":"Hongyan","family":"Li","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330047"]},{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, China, 330052"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"9","key":"2026102109082078000_cit1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.25.33389","article-title":"Hepatocellular Carcinoma:\nA Practical Anatomy-Based Guide for Staging and Treatment Planning,\nFrom the AJR Special Series on Critical Anatomy","volume":"50","author":"Chiu","year":"2025","journal-title":"Am. J. Roentgenol."},{"issue":"5","key":"2026102109082078000_cit2","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/cac2.12543","article-title":"Dietary long-chain fatty acid metabolism boosts antitumor immune\nresponse","volume":"44","author":"Wang","year":"2024","journal-title":"Cancer Commun."},{"key":"2026102109082078000_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101519","article-title":"Selenium deficiency-induced\nredox imbalance leads to metabolic reprogramming and inflammation\nin the liver","volume":"36","author":"Tang","year":"2020","journal-title":"Redox Biol."},{"key":"2026102109082078000_cit4","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1146\/annurev-nutr-062320-121834","article-title":"Dietary\nSelenium Across Species","volume":"42","author":"Lei","year":"2022","journal-title":"Annu. Rev. Nutr."},{"issue":"5","key":"2026102109082078000_cit5","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.70250","article-title":"From Soil to Table:\nA Comprehensive Review of Selenium-Fortified Foods","volume":"24","author":"Li","year":"2025","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"issue":"23","key":"2026102109082078000_cit6","doi-asserted-by":"publisher","first-page":"8731","DOI":"10.1021\/acs.jafc.3c02714","article-title":"Research advances\nin preparation,\nstability, application, and possible risks of nanoselenium: focus\non food and food-related fields","volume":"71","author":"Gao","year":"2023","journal-title":"J. Agric. Food\nChem."},{"issue":"10","key":"2026102109082078000_cit7","doi-asserted-by":"publisher","first-page":"8100","DOI":"10.1021\/acs.jafc.5c17970","article-title":"Advances on\nthe bioactivities, safety, preparation,\nand applications of l-se-methyl-selenocysteine: emphasis on mechanistic\ninsights","volume":"74","author":"Ndayishimiye","year":"2026","journal-title":"J. Agric. Food Chem."},{"issue":"15","key":"2026102109082078000_cit8","doi-asserted-by":"publisher","first-page":"9760","DOI":"10.1021\/acs.analchem.9b01388","article-title":"Addressing complex matrix interference\nimproves multiplex food allergen detection by targeted LC-MS\/MS","volume":"91","author":"Croote","year":"2019","journal-title":"Anal. Chem."},{"key":"2026102109082078000_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2019.125251","article-title":"Targeted UPLC-QqQ-MS\/MS\nprofiling of phenolic compounds for differentiation of monovarietal\nwines and corroboration of particular varietal typicity concepts","volume":"300","author":"Lukic\u0301","year":"2019","journal-title":"Food Chem."},{"key":"2026102109082078000_cit10","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.foodres.2018.12.013","article-title":"Comparison\nassessment between SIM\nand MRM mode in the analysis of 3-MCPD ester, 2-MCPD ester and glycidyl\nester","volume":"121","author":"Goh","year":"2019","journal-title":"Food Res. 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Food Compos. Anal."},{"issue":"41","key":"2026102109082078000_cit14","doi-asserted-by":"publisher","first-page":"22798","DOI":"10.1021\/acs.jafc.4c07225","article-title":"Systematic characterization of the oligosaccharide profile of human\nmilk in rural areas of central China: quantitative tracking of human\nmilk oligosaccharide composition during 12 months of lactation","volume":"72","author":"Zhu","year":"2024","journal-title":"J. Agric. 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Chem.\nLett."},{"issue":"2","key":"2026102109082078000_cit18","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000595","article-title":"Pharmacokinetics\nand ADME characterization of intravenous and oral [14C]-linerixibat\nin healthy male volunteers","volume":"49","author":"Zamek-Gliszczynski","year":"2021","journal-title":"Drug Metab. Dispos."},{"issue":"1","key":"2026102109082078000_cit19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/hep.29499","article-title":"Cystathionine \u03b2-synthase\nis\nrequired for body iron homeostasis","volume":"67","author":"Zhou","year":"2018","journal-title":"Hepatology"},{"issue":"1","key":"2026102109082078000_cit20","doi-asserted-by":"publisher","DOI":"10.1186\/s11671-019-3164-y","article-title":"Preparation and pharmacokinetic\nstudy of daidzein long-circulating liposomes","volume":"14","author":"Wang","year":"2019","journal-title":"Nanoscale Res. Lett."},{"key":"2026102109082078000_cit21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118713","article-title":"Metabolomics and serum\npharmacochemistry combined with network pharmacology uncover the potential\neffective ingredients and mechanisms of Yin-Chen-Si-Ni Decoction treating\nANIT-induced cholestatic liver injury","volume":"335","author":"Liu","year":"2024","journal-title":"J. Ethnopharmacol."},{"issue":"2","key":"2026102109082078000_cit22","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.jia.2023.04.029","article-title":"Metabolic profiles\nand morphological characteristics of leaf tips among different sweet\npotato (Ipomoea batatas Lam.) varieties","volume":"23","author":"Tan","year":"2024","journal-title":"J.\nIntegr. Agric."},{"key":"2026102109082078000_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2025.108744","article-title":"Recent advances\nin\nmicrobial biosynthesis of L-cysteine and its derivative sulfur-containing\nantioxidants","volume":"86","author":"Gao","year":"2026","journal-title":"Biotechnol. 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Nutr."},{"issue":"1","key":"2026102109082078000_cit27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57983-y","article-title":"A general covalent\nbinding model between cytotoxic selenocompounds and albumin revealed\nby mass spectrometry and X-ray absorption spectroscopy","volume":"10","author":"Zheng","year":"2020","journal-title":"Sci. Rep."},{"issue":"5","key":"2026102109082078000_cit28","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1093\/jn\/119.5.706","article-title":"Transport of selenoamino\nacids and their sulfur analogues across the intestinal brush border\nmembrane of pigs","volume":"119","author":"Wolffram","year":"1989","journal-title":"J. Nutr."},{"key":"2026102109082078000_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2021.104914","article-title":"Effects of dietary selenium on immune\nfunction of spleen in mice","volume":"89","author":"Zhang","year":"2022","journal-title":"J. Funct. Foods"},{"issue":"2","key":"2026102109082078000_cit30","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s00216-005-0007-8","article-title":"Selenium metabolites\nin human urine after ingestion of selenite,\nL-selenomethionine, or DL-selenomethionine: a quantitative case study\nby HPLC\/ICPMS","volume":"383","author":"Kuehnelt","year":"2005","journal-title":"Anal. Bioanal. Chem."},{"issue":"7","key":"2026102109082078000_cit31","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.bbagen.2007.03.007","article-title":"Selenocysteine beta-lyase and methylselenol\ndemethylase in the metabolism of Se-methylated selenocompounds into\nselenide","volume":"1770","author":"Suzuki","year":"2007","journal-title":"Biochim. Biophys. Acta, Gen. Subj."},{"issue":"23","key":"2026102109082078000_cit32","doi-asserted-by":"publisher","first-page":"8870","DOI":"10.1039\/c3cs60272a","article-title":"Which form is that? The importance of selenium speciation\nand metabolism in the prevention and treatment of disease","volume":"42","author":"Weekley","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"2026102109082078000_cit33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111844","article-title":"Antitumor effects\nof selenium","volume":"22","author":"Kim","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"11","key":"2026102109082078000_cit34","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfad067","article-title":"Selenomethionine\nsupplementation and expression of selenosugars, selenocysteine, and\nother selenometabolites in rat liver","volume":"15","author":"Bierla","year":"2023","journal-title":"Metallomics"},{"key":"2026102109082078000_cit35","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101322","article-title":"Homocysteine-methionine\ncycle is\na metabolic sensor system controlling methylation-regulated pathological\nsignaling","volume":"28","author":"Shen","year":"2020","journal-title":"Redox Biol."},{"issue":"7","key":"2026102109082078000_cit36","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1038\/s41418-020-0494-3","article-title":"LINC00662\npromotes hepatocellular carcinoma progression via altering genomic\nmethylation profiles","volume":"27","author":"Guo","year":"2020","journal-title":"Cell Death Differ."},{"issue":"10","key":"2026102109082078000_cit37","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12101885","article-title":"Combination\nof cysteine and glutathione prevents ethanol-induced hangover and\nliver damage by modulation of Nrf2 signaling in HepG2 cells and mice","volume":"12","author":"Kim","year":"2023","journal-title":"Antioxidants"},{"issue":"1","key":"2026102109082078000_cit38","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2025.106184","article-title":"Alleviation of taurine on lung injury\nin fatty liver hemorrhagic syndrome laying hens by improving antioxidant\nand anti-inflammatory capacity","volume":"105","author":"Ouyang","year":"2026","journal-title":"Poult. Sci."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c10372","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32410\/68780963\/acs.jafc.6c10372.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32410\/68780963\/acs.jafc.6c10372.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:15:24Z","timestamp":1792588524000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/41\/32410\/5446701\/Evaluation-of-Acute-Pharmacokinetics-and-Liver"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":38,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,10,8]]},"published-print":{"date-parts":[[2026,10,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c10372","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]}}}