title: Cytoprotection of pancreatic β-cells and hypoglycemic effect of 2-hydroxypropyl-β-cyclodextrin: sertraline complex in alloxan-induced diabetic rats.
abstract: Sertraline, a selective inhibitor of serotonin reuptake, is widely used as antidepressant in diabetic patients for improvement of depression and glycemic control. Sertraline is poorly soluble in water, which limits its oral applicability. In this work we tried to improve the pharmaceutical properties of sertraline by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and evaluated the efficacy of the HPβCD:sertraline complex in prevention of alloxan-induced lesions in rats. The solubility of sertraline increased in the presence of HPβCD and the association constant for sertraline and HPβCD was equal to 4000 ± 1000 M(-1). Two-week treatment of diabetic animals with the HPβCD:sertraline complex improved pancreatic islet morphology and β-cell survival, which, in turn, reduced the severity of diabetes, as evidenced by lowering of blood glucose and glycated hemoglobin contents as well as normalization of serum insulin level and insulin sensitivity (HOMA-IR). The effect of the HPβCD:sertraline complex was strongly expressed in comparison with the antidiabetic effect of both the monopreparations, HPβCD and sertraline. It is suggested that the cyclodextrin derivative increased the pharmacological effect of sertraline, probably due to enhanced drug bioavailability.
authors.affiliation: Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, 230030 Grodno, Belarus; Department of Biotechnology, School of Medical Sciences, Krakowska 9, 15-875 Bialystok, Poland. Electronic address: buko@bioch.basnet.by.
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Buko
authors.affiliation: Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, 230030 Grodno, Belarus; Department of Biochemistry, Yanka Kupala Grodno State University, BLK-50, 230030 Grodno, Belarus.
authors.forename: Ilya
authors.initials: I
authors.lastname: Zavodnik
authors.affiliation: Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, 230030 Grodno, Belarus.
authors.forename: Oxana
authors.initials: O
authors.lastname: Lukivskaya
authors.affiliation: Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, 230030 Grodno, Belarus.
authors.forename: Elena
authors.initials: E
authors.lastname: Naruta
authors.affiliation: Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 165, 90-236 Lodz, Poland.
authors.forename: Bartlomiej
authors.initials: B
authors.lastname: Palecz
authors.affiliation: Department of Physical Chemistry, Faculty of Chemistry, University of Lodz, Pomorska 165, 90-236 Lodz, Poland.
authors.forename: Silwia
authors.initials: S
authors.lastname: Belica-Pacha
authors.affiliation: Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK-50, 230030 Grodno, Belarus.
authors.forename: Elena
authors.initials: E
authors.lastname: Belonovskaya
authors.affiliation: Department of Biotechnology, School of Medical Sciences, Krakowska 9, 15-875 Bialystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Kranc
authors.affiliation: Department of Pathological Anatomy, Grodno State Medical University, Gorkogo str., 80, 20009 Grodno, Belarus.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Abakumov
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020280:Sertraline / Q000737:chemistry / Q000494:pharmacology*; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000496:Alloxan; D020280:Sertraline
keywords: 2-Hydroxypropyl-β-cyclodextrin; Alloxan; Diabetes; Insulin; Pancreatic islets; Sertraline