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Metformin is the most commonly used drug for the treatment of type 2 diabetes. Metformin also has potential benefit in cancer prevention and treatment. The aim of this study was to determine whether metformin can directly react with FA and attenuate its toxicity in vitro. Metformin was incubated at pH 7.4 and 37\u00b0C in the presence of FA, and the reaction mixture was analyzed by UV spectrophotometry, high\u2010performance liquid chromatography (HPLC), and mass spectrometry. Fluorescence spectrophotometry, immunofluorescence, and western blot were used to measure FA\u2010induced bovine serum albumin (BSA) crosslinking and DNA damage in HepG2 cells treated with or without metformin. According to the HPLC and mass spectrometry data, we speculate that the reaction of metformin with FA (1:1) initially results in the formation of a conjugated intermediate followed by the subsequent generation of a stable six\u2010membered ring structure. Correspondingly, metformin attenuated FA\u2010induced fluorescence in BSA as well as the aggregation of \u03b3H2AX in HepG2 cells. These results suggest that metformin can protect protein and DNA damage induced by FA at least partly through a direct reaction process.<\/jats:p>","DOI":"10.1002\/tox.22982","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T10:36:40Z","timestamp":1591785400000},"page":"1170-1178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Metformin scavenges formaldehyde and attenuates formaldehyde\u2010induced bovine serum albumin crosslinking and cellular <scp>DNA<\/scp> damage"],"prefix":"10.1002","volume":"35","author":[{"given":"Xinglian","family":"Mai","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital  Qingyuan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of 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