Pharmacological Dose-Effect Profiles of Various Concentrations of Humanised Primary Bile Acid in Encapsulated Cells
Armin Mooranian,
Melissa Jones,
Daniel Walker,
Corina Mihaela Ionescu,
Susbin Raj Wagle,
Bozica Kovacevic,
Jacqueline Chester,
Thomas Foster,
Edan Johnston,
Jafri Kuthubutheen,
Daniel Brown,
Marcus D. Atlas,
Momir Mikov,
Hani Al-Salami
Affiliations
Armin Mooranian
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Melissa Jones
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Daniel Walker
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Corina Mihaela Ionescu
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Susbin Raj Wagle
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Bozica Kovacevic
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Jacqueline Chester
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Thomas Foster
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Edan Johnston
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Jafri Kuthubutheen
Fiona Stanley Hospital, Murdoch, Perth, WA 6150, Australia
Daniel Brown
Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
Marcus D. Atlas
Hearing Therapeutics, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, WA 6009, Australia
Momir Mikov
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21101 Novi Sad, Serbia
Hani Al-Salami
The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, WA 6102, Australia
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.
