Sasse Ryan, Carpenter Nathan, Simpkins Cuthbert O
University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Department of Surgery, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
Free Radic Biol Med. 2025 Feb 1;227:276-281. doi: 10.1016/j.freeradbiomed.2024.12.022. Epub 2024 Dec 5.
Nitric oxide plays a critical role in regulating vascular tone, but excessive nitric oxide release during septic shock results in hypotension due to excessive vasodilation and the formation of toxic free radicals. VBI-S is a phospholipid nanoparticle based fluid composed of lipid bilayers formed primarily by phosphatidylcholine and micelles of soybean oil encapsulated by a monolayer of phosphatidylcholine. These nanoparticles offer a novel solution by absorbing and redistributing nitric oxide and nitrite, potentially mitigating the harmful effects of excessive nitric oxide in sepsis. This paper proposes a mechanism in which VBI-S not only redistributes nitric oxide but also reduces ischemia-reperfusion injury by limiting the production and availability of reactive species. VBI-S captures nitric oxide and nitrite in areas of high concentration and redistributes them in low-nitric oxide environments, primarily within oxygen-deprived tissues. Nitrite then contributes to nitric oxide regeneration in hypoxic microvasculature via various reduction pathways, thereby improving tissue perfusion and minimizing oxidative stress. Preliminary studies suggest that nitrite may also decrease reactive species production, primarily superoxide, through the inhibition of mitochondrial complex I. Additionally, the lipid composition of VBI-S is rich in poly and monounsaturated fatty acids which allows VBI-S to act as a substrate for peroxidation via peroxynitrite. Therefore, VBI-S acts as a decoy target thereby protecting cellular membranes from oxidative damage caused by reactive species. These findings position VBI-S as a promising therapeutic agent, offering both nitric oxide regulation and protection against hypotension and toxic free radicals in septic shock patients. Further research is necessary to fully elucidate the molecular pathways and optimize its clinical application.
一氧化氮在调节血管张力方面起着关键作用，但脓毒性休克期间一氧化氮的过度释放会因血管过度舒张和有毒自由基的形成而导致低血压。VBI-S是一种基于磷脂纳米颗粒的液体，由主要由磷脂酰胆碱形成的脂质双层和被单层磷脂酰胆碱包裹的大豆油微团组成。这些纳米颗粒通过吸收和重新分布一氧化氮和亚硝酸盐提供了一种新的解决方案，有可能减轻脓毒症中一氧化氮过量的有害影响。本文提出了一种机制，其中VBI-S不仅重新分布一氧化氮，还通过限制活性物质的产生和可用性来减少缺血再灌注损伤。VBI-S在高浓度区域捕获一氧化氮和亚硝酸盐，并在低一氧化氮环境中重新分布它们，主要是在缺氧组织内。然后，亚硝酸盐通过各种还原途径促进缺氧微血管中的一氧化氮再生，从而改善组织灌注并最小化氧化应激。初步研究表明，亚硝酸盐还可能通过抑制线粒体复合物I来减少活性物质的产生，主要是超氧化物。此外，VBI-S的脂质成分富含多不饱和脂肪酸和单不饱和脂肪酸，这使得VBI-S能够通过过氧亚硝酸盐作为过氧化的底物。因此，VBI-S充当诱饵靶点，从而保护细胞膜免受活性物质引起的氧化损伤。这些发现使VBI-S成为一种有前景的治疗剂，在脓毒性休克患者中提供一氧化氮调节以及预防低血压和有毒自由基。需要进一步研究以充分阐明分子途径并优化其临床应用。
