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量和其 与人类慢性疾病的关系。众所周知，胖子 不含酸过氧化和脂肪酸氢过氧化氢分解 自由基介导的过程。我们报告了肥胖的活体证据 染毒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)。胖子 A-(4-吡啶-1-氧化物)-N-叔丁基硝酮的酸基加合物 (4-POBN)在体内胆汁标本中检测到。对政府来说 氧化13C-藻类脂肪酸和4-POBN的EPR谱 胆汁中的自由基加合物表现出超精细的偶联 13C。我们的数据表明，以碳为中心的自由基加合物 在活体实验中观察到的明确的来源是氧化 PUFA。这是多不饱和脂肪酸衍生的自由基形成的体内证据 支持这样一种提议，即涉及自由基的过程可能是 先前描述的膳食细胞毒性的分子基础 氧化的多不饱和脂肪酸。 一氧化氮在心脏生理学中发挥着重要作用。 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 在生物样本中，不仅是捕捉活性自由基 但分解产生的一氧化氮可能会发挥作用 在改变生物功能方面发挥重要作用。

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.