Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

General Research Article

Pharmacological Effects of Secondary Bile Acid Microparticles in Diabetic Murine Model

Author(s): Armin Mooranian*, Nassim Zamani, Bozica Kovacevic, Corina Mihaela Ionescu, Giuseppe Luna, Momir Mikov, Svetlana Goločorbin-Kon, Goran Stojanovic, Sanja Kojic and Hani Al-Salami*

Volume 18, Issue 1, 2022

Published on: 26 June, 2020

Article ID: e062620183199 Pages: 10

DOI: 10.2174/1573399816666200626213735

Price: $65

Abstract

Aim: Examine bile acids effects in Type 2 diabetes.

Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent antiinflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma.

Objective: Hence, this study aimed to examine applications of novel UDCA microparticles in diabetes.

Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment.

Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment.

Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

Keywords: Lithocholic acid, metabolites, bile acid profile, diabetes, type 2 diabetes mellitus, nanocapsules.

[1]
Negrulj R, Mooranian A, Al-Salami H. Potentials and Limitations of bile acids in type 2 diabetes mellitus: applications of microencapsulation as a novel oral delivery system. J Endocrinol Diabetes Mellit 2013; 1(2): 49-59.
[2]
Sagar NM, Cree IA, Covington JA, Arasaradnam RP. The interplay of the gut microbiome, bile acids, and volatile organic compounds. Gastroenterol Res Pract 2015.: 2015398585.
[http://dx.doi.org/10.1155/2015/398585] [PMID: 25821460]
[3]
Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol 2014; 30(3): 332-8.
[http://dx.doi.org/10.1097/MOG.0000000000000057] [PMID: 24625896]
[4]
Szpigel A, Hainault I, Carlier A, Venteclef N, Batto AF, Hajduch E, et al. Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes. Diabetologia 2018; 61(2): 399-412.
[PMID: 28988346]
[5]
Kalninova J, Jakus V, Glejtkova M, Kuracka L, Sandorova E. Impact of glycemic control on advanced glycation and inflammation in overweight and obese patients with type 2 diabetes mellitus. Bratisl Lek Listy 2014; 115(8): 457-68.
[http://dx.doi.org/10.4149/BLL_2014_089] [PMID: 25246279]
[6]
Meinders AE, Van Berge Henegouwen GP, Willekens FL, Schwerzel AL, Ruben A, Huybregts AW. Biliary lipid and bile acid composition in insulin-dependent diabetes mellitus. Arguments for increased intestinal bacterial bile acid degradation. Dig Dis Sci 1981; 26(5): 402-8.
[http://dx.doi.org/10.1007/BF01313581] [PMID: 7018861]
[7]
Prawitt J, Caron S, Staels B. Bile acid metabolism and the pathogenesis of type 2 diabetes. Curr Diab Rep 2011; 11(3): 160-6.
[http://dx.doi.org/10.1007/s11892-011-0187-x] [PMID: 21431855]
[8]
Martínez-Moya P, Romero-Calvo I, Requena P, et al. Dose- dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis. Int Immunopharmacol 2013; 15(2): 372-80.
[http://dx.doi.org/10.1016/j.intimp.2012.11.017] [PMID: 23246254]
[9]
Mooranian A, Negrulj R, Al-Salami H, Morahan G, Jamieson E. Designing anti-diabetic β-cells microcapsules using polystyrenic sulfonate, polyallylamine, and a tertiary bile acid: Morphology, bioenergetics, and cytokine analysis. Biotechnol Prog 2016; 32(2): 501-9.
[http://dx.doi.org/10.1002/btpr.2223] [PMID: 26748789]
[10]
Mooranian A, Negrulj R, Al-Sallami HS, et al. Probucol release from novel multicompartmental microcapsules for the oral targeted delivery in type 2 diabetes. AAPS PharmSciTech 2015; 16(1): 45-52.
[http://dx.doi.org/10.1208/s12249-014-0205-9] [PMID: 25168450]
[11]
Mooranian A, Negrulj R, Al-Sallami HS, et al. Release and swelling studies of an innovative antidiabetic-bile acid microencapsulated formulation, as a novel targeted therapy for diabetes treatment. J Microencapsul 2015; 32(2): 151-6.
[http://dx.doi.org/10.3109/02652048.2014.958204] [PMID: 25265061]
[12]
Mooranian A, Negrulj R, Arfuso F, Al-Salami H. The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study. Drug Deliv Transl Res 2015; 5(5): 511-22.
[http://dx.doi.org/10.1007/s13346-015-0248-9] [PMID: 26242686]
[13]
Mooranian A, Negrulj R, Chen-Tan N, Watts GF, Arfuso F. Al- Salami H. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer. Drug Des Devel Ther 2014; 8: 1673-83.
[PMID: 25302020]
[14]
Mooranian A, Zamani N, Takechi R, et al. Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes. Artif Cells Nanomed Biotechnol 2018; 46((sup3)): S748-54.
[http://dx.doi.org/10.1080/21691401.2018.1511572] [PMID: 30422681]
[15]
Mooranian A, Zamani N, Mikov M, et al. Eudragit®-based microcapsules of probucol with a gut-bacterial processed secondary bile acid. Ther Deliv 2018; 9(11): 811-21.
[http://dx.doi.org/10.4155/tde-2018-0036] [PMID: 30444461]
[16]
Mooranian A, Zamani N, Mikov M, et al. Novel nanoencapsulation of probucol in microgels: scanning electron micrograph characterizations, buoyancy profiling, and antioxidant assay analyses. Artif Cells Nanomed Biotechnol 2018; 46((sup3)): S741-7.
[http://dx.doi.org/10.1080/21691401.2018.1511571] [PMID: 30260253]
[17]
Mooranian A, Negrulj R, Takechi R, Mamo J, Al-Sallami H. Al- Salami H. The biological effects of the hypolipidaemic drug probucol microcapsules fed daily for 4 weeks, to an insulin-resistant mouse model: potential hypoglycaemic and anti-inflammatory effects. Drug Deliv Transl Res 2018; 8(3): 543-51.
[http://dx.doi.org/10.1007/s13346-017-0473-5] [PMID: 29313296]
[18]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G. Al- Salami H. Electrokinetic potential-stabilization by bile acidmicroencapsulating formulation of pancreatic β-cells cultured in high ratio poly-L-ornithine-gel hydrogel colloidal dispersion: applications in cell-biomaterials, tissue engineering and biotechnological applications. Artif Cells Nanomed Biotechnol 2018; 46(6): 1156-62.
[http://dx.doi.org/10.1080/21691401.2017.1362416] [PMID: 28776395]
[19]
Takechi R, Lam V, Brook E, et al. Blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: An implication for causal link. Front Aging Neurosci 2017; 9: 399.
[http://dx.doi.org/10.3389/fnagi.2017.00399] [PMID: 29249964]
[20]
Mooranian A, Tackechi R, Jamieson E, Morahan G, Al-Salami H. Innovative microcapsules for pancreatic β-cells harvested from mature double-transgenic mice: Cell imaging, viability, Induced glucose-stimulated insulin measurements and proinflammatory cytokines analysis. Pharm Res 2017; 34(6): 1217-23.
[http://dx.doi.org/10.1007/s11095-017-2138-y] [PMID: 28289997]
[21]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G. Al- Salami H. Alginate-combined cholic acid increased insulin secretion of microencapsulated mouse cloned pancreatic β cells. Ther Deliv 2017; 8(10): 833-42.
[http://dx.doi.org/10.4155/tde-2017-0042] [PMID: 28944743]
[22]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G. Al- Salami H. Influence of biotechnological processes, Speed of formulation flow and cellular concurrent stream-integration on insulin production from β-cells as a result of co-encapsulation with a highly lipophilic bile acid. Cell Mol Bioeng 2017; 11(1): 65-75.
[http://dx.doi.org/10.1007/s12195-017-0510-y] [PMID: 31719879]
[23]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G. Al- Salami H. New biotechnological microencapsulating methodology utilizing individualized gradient-screened jet laminar flow techniques for pancreatic β-cell delivery: Bile acids support cell energy-generating mechanisms. Mol Pharm 2017; 14(8): 2711-8.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00220] [PMID: 28682620]
[24]
Mooranian A, Negrulj R, Al-Salami H. The effects of ionic gelation-vibrational jet flow Technique in fabrication of microcapsules incorporating β-cell: Applications in diabetes. Curr Diabetes Rev 2017; 13(1): 91-6.
[http://dx.doi.org/10.2174/1573399812666151229101756] [PMID: 26710877]
[25]
Mamo JCL, Lam V, Giles C, et al. Antihypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice. Int J Obes 2017; 41(6): 926-34.
[http://dx.doi.org/10.1038/ijo.2017.57] [PMID: 28239165]
[26]
Al-Salami H, Mamo JC, Mooranian A, et al. Long-term supplementation of microencapsulated ursodeoxycholic acid prevents hypertension in a mouse model of insulin resistance. Exp Clin Endocrinol Diabetes 2017; 125(1): 28-32.
[PMID: 27219878]
[27]
Mooranian A, Negrulj R, Jamieson E, Morahan G, Al-Salami H. Biological assessments of encapsulated pancreatic β-cells: Their potential transplantation in diabetes. Cell Mol Bioeng 2016; 9(4): 530-7.
[http://dx.doi.org/10.1007/s12195-016-0441-z]
[28]
Al-Salami H, Butt G, Tucker I, Mikov M. Influence of the semisynthetic bile acid (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats. Methods Find Exp Clin Pharmacol 2008; 30(2): 107-13.
[http://dx.doi.org/10.1358/mf.2008.30.2.1159652] [PMID: 18560625]
[29]
Al-Salami H, Butt G, Tucker I, Golocorbin-Kon S, Mikov M. Probiotics decreased the bioavailability of the bile acid analog, monoketocholic acid, when coadministered with gliclazide, in healthy but not diabetic rats. Eur J Drug Metab Pharmacokinet 2012; 37(2): 99-108.
[http://dx.doi.org/10.1007/s13318-011-0060-y] [PMID: 21874525]
[30]
Mooranian A, Negrulj R, Takechi R, Mamo JC, Al-Sallami H. Al- Salami H. The biological effects of the hypolipidaemic drug probucol incorporated into bile acid-microcapsules and fed daily for 4- weeks, to an insulin-resistant mouse model: Potential hypoglycaemic and anti-inflammatory effects. Drug Deliv Transl Res In press
[31]
Mooranian A, Negrulj R, Al-Salami H. Primary bile acid chenodeoxycholic acid-based microcapsules to examine β-cell survival and the inflammatory response. Bionanoscience 2016; 6(2): 103-9.
[http://dx.doi.org/10.1007/s12668-016-0198-9]
[32]
Mooranian A, Negrulj R, Al-Salami H. The impact of allylaminebile acid combinations on cell delivery microcapsules in diabetes. J Microencapsul 2016; 33(6): 569-74.
[http://dx.doi.org/10.1080/02652048.2016.1228703] [PMID: 27574968]
[33]
Mooranian A, Negrulj R, Al-Salami H. Viability and topographical analysis of microencapsulated β-cells exposed to a biotransformed tertiary bile acid: An ex vivo study. Int J Nano Biomaterials 2016; 6(2): 74-82.
[http://dx.doi.org/10.1504/IJNBM.2016.079684]
[34]
Lukivskaya O, Patsenker E, Buko VU. Protective effect of ursodeoxycholic acid on liver mitochondrial function in rats with alloxaninduced diabetes: link with oxidative stress. Life Sci 2007; 80(26): 2397-402.
[http://dx.doi.org/10.1016/j.lfs.2007.02.042] [PMID: 17512017]
[35]
Lukivskaya O, Lis R, Egorov A, Naruta E, Tauschel HD, Buko VU. The protective effect of ursodeoxycholic acid in alloxaninduced diabetes. Cell Biochem Funct 2004; 22(2): 97-103.
[http://dx.doi.org/10.1002/cbf.1063] [PMID: 15027098]
[36]
Brites D, Rodrigues CM, Oliveira N, Cardoso M, Graça LM. Correction of maternal serum bile acid profile during ursodeoxycholic acid therapy in cholestasis of pregnancy. J Hepatol 1998; 28(1): 91-8.
[http://dx.doi.org/10.1016/S0168-8278(98)80207-9] [PMID: 9537870]
[37]
Shen A. A Gut Odyssey: The impact of the microbiota on clostridium difficile spore formation and germination. PLoS Pathog 2015; 11(10): e1005157.
[http://dx.doi.org/10.1371/journal.ppat.1005157] [PMID: 26468647]
[38]
Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J 2006; 25(7): 1419-25.
[http://dx.doi.org/10.1038/sj.emboj.7601049] [PMID: 16541101]
[39]
Zollner G, Fickert P, Fuchsbichler A, et al. Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine. J Hepatol 2003; 39(4): 480-8.
[http://dx.doi.org/10.1016/S0168-8278(03)00228-9] [PMID: 12971955]
[40]
Al-Salami H, Butt G, Tucker I, Mikov M. Influence of the semisynthetic bile acid (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats. Pharmacol Rep 2008; 60(4): 532-41.
[PMID: 18799822]
[41]
Nishida S, Ozeki J, Makishima M. Modulation of bile acid metabolism by 1alpha-hydroxyvitamin D3 administration in mice. Drug Metab Dispos 2009; 37(10): 2037-44.
[http://dx.doi.org/10.1124/dmd.109.027334] [PMID: 19581390]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy