Formaldehyde (FA) can be produced in the environment and by cell metabolism and has been classified as a carcinogen in animals and humans. 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°C in the presence of FA, and the reaction mixture was analyzed by UV spectrophotometry, high‐performance liquid chromatography (HPLC), and mass spectrometry. Fluorescence spectrophotometry, immunofluorescence, and western blot were used to measure FA‐induced 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‐membered ring structure. Correspondingly, metformin attenuated FA‐induced fluorescence in BSA as well as the aggregation of γH2AX 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.

中文翻译：

---

二甲双胍清除甲醛并减轻甲醛诱导的牛血清白蛋白交联和细胞 DNA 损伤

甲醛 (FA) 可在环境和细胞代谢中产生，已被归类为动物和人类的致癌物。二甲双胍是治疗2型糖尿病最常用的药物。二甲双胍还具有预防和治疗癌症的潜在益处。本研究的目的是确定二甲双胍是否可以直接与 FA 反应并在体外减弱其毒性。在 FA 存在下，将二甲双胍在 pH 7.4 和 37°C 下孵育，并通过紫外分光光度法、高效液相色谱法 (HPLC) 和质谱法分析反应混合物。荧光分光光度法、免疫荧光法和蛋白质印迹法用于测量用或不用二甲双胍处理的 HepG2 细胞中 FA 诱导的牛血清白蛋白 (BSA) 交联和 DNA 损伤。根据 HPLC 和质谱数据，我们推测二甲双胍与 FA (1:1) 的反应最初导致形成共轭中间体，随后生成稳定的六元环结构。相应地，二甲双胍减弱了 BSA 中 FA 诱导的荧光以及 HepG2 细胞中 γH2AX 的聚集。这些结果表明二甲双胍可以至少部分通过直接反应过程保护由 FA 诱导的蛋白质和 DNA 损伤。