IN VIVO DETECTION OF FREE RADICALS AND NITRIC OXIDE IN TOXICITY

许多研究都集中在高膳食脂肪摄入及其 与人类慢性疾病的关系。 众所周知，脂肪 酸过氧化和脂肪酸氢过氧化物分解是免费的 激进分子介导的过程。 我们报告了体内证据， 给药大鼠胆汁中酸源性自由基代谢产物的形成 自旋陷阱和氧化多不饱和脂肪酸（PUFA）。 脂肪 α-（4-吡啶基-1-氧化物）-N-叔丁基硝酮的酸衍生自由基加合物 （4-POBN）在体内胆汁样品中检测到。 在行政 氧化的13 C-藻类脂肪酸和4-POBN的EPR谱， 胆汁中存在的自由基加合物表现出超精细耦合， 13 C.我们的数据表明碳中心自由基加合物 在体内实验中观察到的结果明确来源于氧化 PUFA。 PUFA衍生的自由基形成的体内证据 支持的建议，涉及自由基的过程可能是 先前描述的膳食纤维细胞毒性的分子基础 氧化PUFA。 一氧化氮在机体的生理功能中起着重要的作用， 心血管免疫和神经系统 我们的研究表明， 自旋陷阱PBN或4-POBN可能是一氧化氮的来源 在生物环境中。 当利用这些硝酮作为自旋陷阱时 在生物样品中，不仅是捕获活性自由基， 有效，但分解产生的一氧化氮可能起作用， 改变生物功能的重要作用。

Numerous studies have focused on high dietary fat intake and its association with chronic diseases in humans. It is well known that fatty acid peroxidation and fatty acid hydroperoxide decomposition are free radical-mediated processes. We report in vivo evidence for fatty acid-derived free radical metabolite formation in bile of rats dosed with spin traps and oxidized polyunsaturated fatty acids (PUFA). Fatty acid-derived radical adducts of a-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN) were detected in vivo in bile samples. Upon the administration of oxidized 13C-algal fatty acids and 4-POBN, the EPR spectrum of the radical adducts present in the bile exhibited hyperfine couplings due to 13C. Our data demonstrate that the carbon-centered radical adducts observed in in vivo experiments are unequivocally derived from oxidized PUFA. This in vivo evidence for PUFA-derived free radical formation supports the proposal that processes involving free radicals may be the molecular basis for the previously described cytotoxicity of dietary oxidized PUFA. Nitric oxide plays very important functions in the physiology of cardiovascular, immune and nervous systems. Our study suggests the possibility that spin traps, PBN or 4-POBN, may be sources of nitric oxide in biological environments. When utilizing these nitrones as spin traps in biological samples, not only is the trapping of reactive free radicals operative, but nitric oxide produced from the decomposition may play an important role in altering biological functions.