Hassoun E A, Bagchi D, Bagchi M, Stohs S J
School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Free Radic Biol Med. 1995 Mar;18(3):577-83. doi: 10.1016/0891-5849(94)00156-e.
Previous studies have shown that an aqueous smokeless tobacco extract when administered in a single oral dose to rats results in an enhanced induction of hepatic lipid peroxidation, hepatic DNA single strand breaks, and a marked increase in the urinary excretion of the lipid metabolites malondialdehyde, formaldehyde, acetaldehyde, and acetone. These observations strongly suggest that STE induces the production of reactive oxygen species. We have therefore examined the effects of STE in vivo in rats on the production of nitric oxide (NO) by isolated peritoneal exudate (macrophage) cells and when incubated with cultured J774A.1 macrophage cells. In both cases, a significant increase in NO production was observed. When the antioxidant vitamin E succinate was preadministered to rats, a marked decrease in NO production in response to STE by isolated peritoneal macrophages was observed. Similar results were observed when J774A.1 macrophages were cultured in the presence of vitamin E succinate and STE. When vitamin E succinate alone was cultured with macrophages, an increase in NO production was observed. A similar increase was observed when the vitamin E succinate was administered to rats, and NO production by isolated peritoneal macrophages was assessed. The results demonstrated that the increase in NO production by macrophages in response to vitamin E succinate was due to a succinate moiety. Taken together with previous studies, the results indicate that STE activates macrophages, which result in the production of reactive oxygen species. These reactive oxygen species may be responsible for tissue damaging effects including lipid peroxidation and DNA damage, which may be associated with the cytotoxicity and mutagenicity of smokeless tobacco products.
先前的研究表明，将水基无烟烟草提取物以单次口服剂量给予大鼠后，会增强肝脏脂质过氧化、肝脏DNA单链断裂的诱导作用，并使脂质代谢产物丙二醛、甲醛、乙醛和丙酮的尿排泄量显著增加。这些观察结果强烈表明，无烟烟草提取物可诱导活性氧的产生。因此，我们研究了无烟烟草提取物在大鼠体内对分离的腹腔渗出液（巨噬细胞）产生一氧化氮（NO）的影响，以及与培养的J774A.1巨噬细胞一起孵育时的影响。在这两种情况下，均观察到NO产生显著增加。当预先给大鼠施用抗氧化剂维生素E琥珀酸酯时，观察到分离的腹腔巨噬细胞对无烟烟草提取物反应产生的NO显著减少。当在维生素E琥珀酸酯和无烟烟草提取物存在的情况下培养J774A.1巨噬细胞时，观察到了类似的结果。当单独用维生素E琥珀酸酯与巨噬细胞一起培养时，观察到NO产生增加。当给大鼠施用维生素E琥珀酸酯并评估分离的腹腔巨噬细胞产生的NO时，也观察到了类似的增加。结果表明，巨噬细胞对维生素E琥珀酸酯反应产生的NO增加是由于琥珀酸部分所致。与先前的研究结果一起，这些结果表明无烟烟草提取物激活巨噬细胞，从而导致活性氧的产生。这些活性氧可能是包括脂质过氧化和DNA损伤在内的组织损伤效应的原因，这可能与无烟烟草产品的细胞毒性和致突变性有关。
