Giri S N, Blaisdell R, Rucker R B, Wang Q, Hyde D M
Department of Molecular Biosciences, University of California, Davis 95616.
Environ Health Perspect. 1994 Dec;102 Suppl 10(Suppl 10):137-47. doi: 10.1289/ehp.94102s10137.
Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans.
经气管内注入博来霉素(BL)诱导的间质性肺纤维化涉及活性氧的过量产生、缺乏足够水平的烟酰胺腺嘌呤二核苷酸(NAD)和三磷酸腺苷(ATP)来修复受损的肺上皮细胞,以及肺胶原蛋白反应过度旺盛,随后沉积高度交联的成熟胶原纤维,这些纤维对酶降解具有抗性。在本研究中,我们已经证明,在多剂量BL仓鼠模型中,饮食中补充牛磺酸和烟酸几乎能完全预防肺纤维化。牛磺酸和烟酸的保护作用机制是多方面的。这些机制包括牛磺酸清除次氯酸(HOCl)和稳定生物膜的能力;烟酸补充BL诱导的NAD和ATP消耗的能力;以及牛磺酸和烟酸联合抑制BL诱导的肺胶原蛋白反应性增加各方面的作用,这是间质性肺纤维化的一个标志。根据本次会议展示的数据得出结论,牛磺酸和烟酸联合治疗提供了一种多管齐下的方法,在干预动物和人类化学诱导的间质性肺纤维化发展方面将具有巨大的治疗潜力。