Abstract：
There is a pressing need for novel pharmacological interventions and drug delivery innovations to attenuate the cigarette smoke-associated oxidative stress and lung disease. We report here on the attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and metabolomics of Wistar rats exposed to cigarette smoke for 28 days. The animals were treated for 15 days with plain cysteamine given orally or cysteamine as nanoemulsion given orally or via inhalation. The study design also included two control groups as follows: rats exposed to cigarette smoke but did not receive a treatment (diseased control group) and rats neither exposed to cigarette smoke nor a treatment (normal control group). The targeted metabolomics using Parallel Reaction Monitoring showed that in the diseased control group, ornithine, nicotinamide, xanthine, hypoxanthine, and caprolactam were increased compared with the normal control group. In addition, (±)8(9)-DiHET, which was initially downregulated in the diseased control group, exhibited a reversal of this trend with cysteamine nanoemulsion given via inhalation. The cysteamine nanoemulsion delivered by inhalation highlighted the importance of the route of drug administration for targeting the lungs. To the best of our knowledge, this is the first work to use ATR-FTIR and metabolomics in Wistar rat lung tissues, suggesting how cysteamine nanoemulsion can potentially reduce cigarette smoke-induced oxidative damage. The metabolites reported herein have potential implications for discovery of novel theranostics and, thus, to cultivate diagnostic and therapeutic innovation for early prevention and treatment of cigarette smoke-associated lung diseases.
摘要：
迫切需要新的药理学干预和药物递送创新以减弱香烟烟雾相关的氧化应激和肺部疾病。我们在此报告了暴露于香烟烟雾28天的Wistar大鼠的衰减全反射-傅立叶变换红外光谱（ATR-FTIR）和代谢组学。用口服给予的普通半胱胺或口服或通过吸入给予的纳米乳剂半胱胺治疗动物15天。研究设计还包括如下两个对照组:暴露于香烟烟雾但不接受治疗的大鼠(患病对照组)和既不暴露于香烟烟雾也不接受治疗的大鼠(正常对照组)。基于平行反应监测的靶向代谢组学研究表明,在疾病对照组中,鸟氨酸,烟酰胺,黄嘌呤,次黄嘌呤,与正常对照组相比，己内酰胺增加。此外,(±)8(9)-DiHET,最初在患病对照组中下调，通过吸入给予半胱胺纳米乳剂表现出这种趋势的逆转。通过吸入递送的半胱胺纳米乳剂强调了靶向肺的药物施用途径的重要性。据我们所知,这是首次在Wistar大鼠肺组织中使用ATR-FTIR和代谢组学，提示半胱胺纳米乳液如何潜在地减少香烟烟雾引起的氧化损伤。本文报道的代谢物对发现新的theranosics和，因此，培养早期预防和治疗香烟烟雾相关肺部疾病的诊断和治疗创新。
