不同浓度人源化初级胆汁酸在包封细胞中的药理剂量效应曲线

Pharmacological Dose-Effect Profiles of Various Concentrations of Humanised Primary Bile Acid in Encapsulated Cells.

作者信息

Mooranian Armin, Jones Melissa, Walker Daniel, Ionescu Corina Mihaela, Wagle Susbin Raj, Kovacevic Bozica, Chester Jacqueline, Foster Thomas, Johnston Edan, Kuthubutheen Jafri, Brown Daniel, Atlas Marcus D, Mikov Momir, Al-Salami Hani

机构信息

The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia.

Hearing Therapeutics, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, WA 6009, Australia.

出版信息

Nanomaterials (Basel). 2022 Feb 15;12(4):647. doi: 10.3390/nano12040647.

Abstract

Bile acids (BA)s are known surfactants and well-documented to play a major role in food digestion and absorption. Recently, potential endocrinological and formulation-stabilisation effects of BAs have been explored and their pharmacological effects on supporting cell survival and functions have gained wide interest. Hence, this study aimed to explore the hyper-glycaemic dependent dose-effect of the BA chenodeoxycholic acid (CDCA) when encapsulated with pancreatic β-cells, allowing assessment of CDCA's impacts when encapsulated. Four different concentrations of the BA were prepared, and viable cells were encapsulated and incubated for 2 days. Multiple analyses were carried out including confocal imaging, glucose-induced cellular mitochondrial viability indices, insulin production, inflammatory biomarker analyses and cellular bioenergetics measurements. There was a significant dose-effect with different concentrations of the BA, affecting cellular viability and antioxidant activities, cell functions and insulin release, inflammatory biomarkers, and cellular-bioenergetics at different oxidative stress levels. The results demonstrate that, when encapsulated, the BA CDCA exerts positive pharmacological effects at the cellular level, and such effects are concentration dependent.

摘要

胆汁酸(BAs)是已知的表面活性剂,并且有充分文献记载其在食物消化和吸收中起主要作用。最近,人们探索了胆汁酸的潜在内分泌和制剂稳定化作用,并且它们对支持细胞存活和功能的药理作用已引起广泛关注。因此,本研究旨在探讨当与胰腺β细胞封装在一起时,胆汁酸鹅去氧胆酸(CDCA)的高血糖依赖性剂量效应,以便评估封装时CDCA的影响。制备了四种不同浓度的胆汁酸,将活细胞进行封装并孵育2天。进行了多项分析,包括共聚焦成像、葡萄糖诱导的细胞线粒体活力指数、胰岛素分泌、炎症生物标志物分析和细胞生物能量学测量。不同浓度的胆汁酸存在显著的剂量效应,在不同的氧化应激水平下影响细胞活力和抗氧化活性、细胞功能和胰岛素释放、炎症生物标志物以及细胞生物能量学。结果表明,当封装时,胆汁酸CDCA在细胞水平上发挥积极的药理作用,并且这种作用是浓度依赖性的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdfc/8879575/2cb6bce342da/nanomaterials-12-00647-g001.jpg

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