title: Modified hydroxyethyl starch protects cells from oxidative damage.
abstract: This article describes the synthesis of novel starch-antioxidant conjugates, which show great potential for biomedical applications to protect cells from oxidative damage. These conjugates were synthesized by the modification of a hydroxyethyl starch (molecular weight=200,000g/mol) with various sterically hindered phenols that differ in radical scavenging activity. They possess substantial radical scavenging activity toward a model free radical. It was found that the polymer conjugate conformation depends on the antioxidant structure and degree of substitution. We constructed the complete conformational phase behavior for the polymers with increasing degrees of substitution from small-angle neutron scattering data. It was observed that the conjugate conformation changes are the result of water shifting from a thermodynamically favorable solvent to an unfavorable one, a process that then leads to compaction of the conjugate. We selected the conjugates that possess high substitution degree but still exhibit coil conformation for biological studies. The high efficiency of the conjugates was confirmed by different in vitro (hypotonic hemolysis of erythrocytes/osmotic resistance of erythrocytes and the change of [Ca(2+)]i inside freshly isolated cardiomyocytes) and in vivo (acute hemorrhage/massive blood loss) methods.
authors.affiliation: Institute of Macromolecular Chemistry, AS CR, Heyrovsky Sq. 2, Prague 6, Prague 162 06, Czech Republic. Electronic address: sfill225@gmail.com.
authors.forename: Sergey K
authors.initials: SK
authors.lastname: Filippov
authors.affiliation: Institute of Chemistry, St. Petersburg State University, Russia.
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Sergeeva
authors.affiliation: Institute of Chemistry, St. Petersburg State University, Russia.
authors.forename: Petr S
authors.initials: PS
authors.lastname: Vlasov
authors.affiliation: Institute of Chemistry, St. Petersburg State University, Russia.
authors.forename: Margarita S
authors.initials: MS
authors.lastname: Zavyalova
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Petersburg, Russia.
authors.forename: Galina B
authors.initials: GB
authors.lastname: Belostotskaya
authors.affiliation: Helmholz-Zentrum Geesthacht: Zentrum für Material und Küstenforschung GmbH, DE-21502 Geesthacht, Germany.
authors.forename: Vasil M
authors.initials: VM
authors.lastname: Garamus
authors.affiliation: North-West Federal Medical Research Centre, St. Petersburg, Russia.
authors.forename: Raisa S
authors.initials: RS
authors.lastname: Khrustaleva
authors.affiliation: Institute of Macromolecular Chemistry, AS CR, Heyrovsky Sq. 2, Prague 6, Prague 162 06, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Stepanek
authors.affiliation: Institute of Chemistry, St. Petersburg State University, Russia. Electronic address: ninadomnina@mail.ru.
authors.forename: Nina S
authors.initials: NS
authors.lastname: Domnina
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D010952:Plasma Substitutes / Q000737:chemistry* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D006895:Hydroxyethyl Starch Derivatives; D010636:Phenols; D010952:Plasma Substitutes
keywords: Antioxidant; Conformation; Hydroxyethyl starch; Oxidative damage; Oxidative stress; SANS; Volume expander