Armin Mooranian1, Nassim Zamani1, Ryu Takechi2, Hesham Al-Sallami3, Momir Mikov4, Svetlana Goločorbin-Kon5, Bozica Kovacevic5, Frank Arfuso6, Hani Al-Salami1. 1. a Biotechnology and Drug Development Research Laboratory, School of Pharmacy and Biomedical Sciences , Curtin Health Innovation Research Institute, Curtin University , Perth , Australia. 2. b School of Public Health , Curtin Health Innovation Research Institute, Curtin University , Perth , Australia. 3. c School of Pharmacy , University of Otago , Dunedin , New Zealand. 4. d Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine , University of Novi Sad , Novi Sad , Serbia. 5. e Department of Pharmacy , University of Novi Sad , Novi Sad , Serbia. 6. f Stem Cell and Cancer Biology Laboratory, School of Pharmacy and Biomedical Sciences , Curtin Health Innovation Research Institute, Curtin University , Perth , Australia.
Abstract
INTRODUCTION: The ratio of secondary to primary bile acids changes during Type 1 Diabetes (T1D) development and these effects might be ameliorated by using cholesterol lowering drugs or hydrophilic bile acids. Probucol is a cholesterol-lowering drug, while ursodeoxycholic acid is a hydrophilic bile acid. This study investigated whether nanoencapsulated probucol with ursodeoxycholic acid altered bile acid ratios and the development of diabetes. METHODS: Balb/c mice were divided into three groups and gavaged daily with either free probucol, nanoencapsulated probucol or nanoencapsulated probucol with ursodeoxycholic acid for seven days. Alloxan was injected and once T1D was confirmed the mice continued to receive daily gavages until euthanasia. Blood, tissues, faeces and urine were collected for analysis of insulin and bile acids. RESULTS AND CONCLUSIONS: Nanoencapsulated probucol-ursodeoxycholic acid resulted in significant levels of insulin in the blood, lower levels of secondary bile acids in liver and lower levels of primary bile acids in brain, while ratio of secondary to primary bile acids remains similar among all groups, except in the faeces. Findings suggests that nanoencapsulated probucol-ursodeoxycholic acid may exert a protective effect on pancreatic β-cells and reserve systemic insulin load via modulation of bile acid concentrations in the liver and brain.
INTRODUCTION: The ratio of secondary to primary bile acids changes during Type 1 Diabetes (T1D) development and these effects might be ameliorated by using cholesterol lowering drugs or hydrophilic bile acids. Probucol is a cholesterol-lowering drug, while ursodeoxycholic acid is a hydrophilic bile acid. This study investigated whether nanoencapsulated probucol with ursodeoxycholic acid altered bile acid ratios and the development of diabetes. METHODS: Balb/c mice were divided into three groups and gavaged daily with either free probucol, nanoencapsulated probucol or nanoencapsulated probucol with ursodeoxycholic acid for seven days. Alloxan was injected and once T1D was confirmed the mice continued to receive daily gavages until euthanasia. Blood, tissues, faeces and urine were collected for analysis of insulin and bile acids. RESULTS AND CONCLUSIONS: Nanoencapsulated probucol-ursodeoxycholic acid resulted in significant levels of insulin in the blood, lower levels of secondary bile acids in liver and lower levels of primary bile acids in brain, while ratio of secondary to primary bile acids remains similar among all groups, except in the faeces. Findings suggests that nanoencapsulated probucol-ursodeoxycholic acid may exert a protective effect on pancreatic β-cells and reserve systemic insulin load via modulation of bile acid concentrations in the liver and brain.
Authors: Armin Mooranian; Thomas Foster; Corina M Ionescu; Louise Carey; Daniel Walker; Melissa Jones; Susbin Raj Wagle; Bozica Kovacevic; Jacqueline Chester; Edan Johnstone; Jafri Kuthubutheen; Daniel Brown; Marcus D Atlas; Momir Mikov; Hani Al-Salami Journal: Drug Des Devel Ther Date: 2021-10-23 Impact factor: 4.162