Deol Poonamjot, Yang Jun, Morisseau Christophe, Hammock Bruce D, Sladek Frances M
Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, CA, United States.
Department of Entomology and Nematology and UCD Comprehensive Cancer Center, University of California, Davis, Davis, CA, United States.
Front Pharmacol. 2019 May 29;10:580. doi: 10.3389/fphar.2019.00580. eCollection 2019.
Dimethylsulfoxide (DMSO) is widely used as a solvent and cryopreservative in laboratories and considered to have many beneficial health effects in humans. Oxylipins are a class of biologically active metabolites of polyunsaturated fatty acids (PUFAs) that have been linked to a number of diseases. In this study, we investigated the effect of DMSO on oxylipin levels in mouse liver. Liver tissue from male mice (C57Bl6/N) that were either untreated or injected with 1% DMSO at 18 weeks of age was analyzed for oxylipin levels using ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A decrease in oxylipin diols from linoleic acid (LA, C18:2n6), alpha-linolenic acid (ALA, C18:3n3) and docosahexeanoic acid (DHA, C22:6n3) was observed 2 h after injection with DMSO. In contrast, DMSO had no effect on the epoxide precursors or other oxylipins including those derived from arachidonic acid (C20:4n6) or eicosapentaenoic acid (EPA, C20:5n3). It also did not significantly affect the diol:epoxide ratio, suggesting a pathway distinct from, and potentially complementary to, soluble epoxide hydrolase inhibitors (sEHI). Since oxylipins have been associated with a wide array of pathological conditions, from arthritis pain to obesity, our results suggest one potential mechanism underlying the apparent beneficial health effects of DMSO. They also indicate that caution should be used in the interpretation of results using DMSO as a vehicle in animal experiments.
二甲基亚砜(DMSO)在实验室中被广泛用作溶剂和冷冻保护剂,并被认为对人体健康有许多有益影响。氧化脂质是一类多不饱和脂肪酸(PUFA)的生物活性代谢产物,与多种疾病有关。在本研究中,我们调查了DMSO对小鼠肝脏中氧化脂质水平的影响。使用超高效液相色谱串联质谱法(UPLC-MS/MS)分析了18周龄时未处理或注射1%DMSO的雄性小鼠(C57Bl6/N)的肝脏组织中的氧化脂质水平。注射DMSO后2小时,观察到来自亚油酸(LA,C18:2n6)、α-亚麻酸(ALA,C18:3n3)和二十二碳六烯酸(DHA,C22:6n3)的氧化脂质二醇减少。相比之下,DMSO对环氧化物前体或其他氧化脂质没有影响,包括那些源自花生四烯酸(C20:4n6)或二十碳五烯酸(EPA,C20:5n3)的氧化脂质。它也没有显著影响二醇与环氧化物的比例,表明其途径与可溶性环氧化物水解酶抑制剂(sEHI)不同,可能具有互补性。由于氧化脂质与从关节炎疼痛到肥胖等一系列病理状况有关,我们的结果提示了DMSO明显有益健康影响的一种潜在机制。它们还表明,在动物实验中使用DMSO作为载体解释结果时应谨慎。