Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat

Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are...

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Main Authors: Mladena Lalić-Popović, Velibor Vasović, Boris Milijašević, Svetlana Goločorbin-Kon, Hani Al-Salami, Momir Mikov
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2013/598603
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author Mladena Lalić-Popović
Velibor Vasović
Boris Milijašević
Svetlana Goločorbin-Kon
Hani Al-Salami
Momir Mikov
author_facet Mladena Lalić-Popović
Velibor Vasović
Boris Milijašević
Svetlana Goločorbin-Kon
Hani Al-Salami
Momir Mikov
author_sort Mladena Lalić-Popović
collection DOAJ
description Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Twenty-four male Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB.
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series Journal of Diabetes Research
spelling doaj-art-92a08e7465414909a9a12daa8ae601e52025-02-03T06:12:22ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/598603598603Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a RatMladena Lalić-Popović0Velibor Vasović1Boris Milijašević2Svetlana Goločorbin-Kon3Hani Al-Salami4Momir Mikov5Department of Pharmacy, Medical Faculty, University of Novi Sad, 2100 Novi Sad, SerbiaDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty, University of Novi Sad, 2100 Novi Sad, SerbiaDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty, University of Novi Sad, 2100 Novi Sad, SerbiaDepartment of Pharmacy, Medical Faculty, University of Novi Sad, 2100 Novi Sad, SerbiaSchool of Pharmacy, Curtin University, Perth, WA 6845, AustraliaDepartment of Pharmacology, Toxicology and Clinical Pharmacology, Medical Faculty, University of Novi Sad, 2100 Novi Sad, SerbiaMajor problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Twenty-four male Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB.http://dx.doi.org/10.1155/2013/598603
spellingShingle Mladena Lalić-Popović
Velibor Vasović
Boris Milijašević
Svetlana Goločorbin-Kon
Hani Al-Salami
Momir Mikov
Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat
Journal of Diabetes Research
title Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat
title_full Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat
title_fullStr Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat
title_full_unstemmed Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat
title_short Deoxycholic Acid as a Modifier of the Permeation of Gliclazide through the Blood Brain Barrier of a Rat
title_sort deoxycholic acid as a modifier of the permeation of gliclazide through the blood brain barrier of a rat
url http://dx.doi.org/10.1155/2013/598603
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