title: New cationically modified pullulan attenuates atherogenesis and influences lipid metabolism in apoE-knockout mice.
abstract: Pullulan is a biocompatible polysaccharide obtained from black, yeast-like fungus Aureobasidium pullulans. This polymer is used to deliver various substances to the liver because of its specificity for this organ. Pullulan is internalized into hepatocytes in the process of asialoglycoprotein receptor mediated endocytosis. Recently, by reaction with glycidyltrimethylammonium chloride (GTMAC) we have successfully synthesized a cationically-modified pullulan (Pull-GTMAC). Pull-GTMAC exhibits some unique beneficial effects not found for its native counterpart. In this article we have reported for the first time that Pull-GTMAC administered orally to apoE-knockout mice (murine model of atherosclerosis) at a dose of 300 mg/kg b.w./day for 18 weeks showed anti-atherosclerotic activity reducing the area of atherosclerotic plaque. We have also found that Pull-GTMAC at a dose of 300 mg/kg b.w./day increases both the average daily mass of feces and the average number of droppings excreted by apoE(-/-) mouse in relation to the control sample derived from the mice fed with feed without the tested compound. However, the raw fat content in the feces of apoE-knockout mice was decreased in the group fed with the diet containing Pull-GTMAC towards control group of animals. Pull-GTMAC caused also statistically significant increase of mRNA level for LDL receptor in the apoE(-/-) mice liver after administration at a dose of 300 mg/kg/b.w./day for 18 weeks. However, the compound had no impact on lipid profile in serum of the tested mice. What is more, the studies on HepG2 cell line indicated an antiproliferative potential of cationically modified pullulan after 24 hour and 48 hour of incubation with the polysaccharide. In this paper we have shown for first time that cationically modified pullulan has antiatherogenic potential and influences on lipid metabolism.
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland. joanna.stefan@uj.edu.pl.
authors.forename: J
authors.initials: J
authors.lastname: Stefan
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kus
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wisniewska
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Cracow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kaminski
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Cracow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Szczubialka
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Jawien
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Cracow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Nowakowska
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, Cracow, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004852:Epoxy Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005936:Glucans / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D004852:Epoxy Compounds; D005936:Glucans; D000644:Quaternary Ammonium Compounds; D011973:Receptors, LDL; C045006:glycidyl trimethylammonium; C009109:pullulan