dc.creator | Hassan, Waseem | |
dc.date.accessioned | 2022-03-24T10:47:14Z | |
dc.date.available | 2022-03-24T10:47:14Z | |
dc.date.issued | 2009 | |
dc.identifier.uri | http://repositorio.ufsm.br/handle/1/23868 | |
dc.description.abstract | ----- | eng |
dc.description.sponsorship | Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq | por |
dc.description.sponsorship | Academy of Sciences for Third World - TWAS | por |
dc.language | eng | por |
dc.publisher | Universidade Federal de Santa Maria | por |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Organochalcogens | eng |
dc.subject | pH | eng |
dc.subject | Anti-oxidant activity | eng |
dc.subject | Thiols | eng |
dc.title | Influence of pH on the reactivity of organochalcogens with thiols of biological significance and anti-oxidant potential In rat’s tissue and phospholipid extracts | por |
dc.type | Tese | por |
dc.description.resumo | This study provides experimental data about the anti-oxidant activity of diphenyl diselenide,
diphenyl ditelluride, a novel organoselenium compound and ebselen under various pH
conditions. Iron is more soluble at lower pH values; therefore we hypothesized that
decreasing the environmental pH would lead to increased iron-mediated lipid peroxidation.
Because of the pH dependency of iron redox cycling, pH and iron need to be well
controlled and for the reason we tested a number of pH values (from 7.4 to 5.4) to get a
closer idea about the role of iron under various pathological conditions. Acidosis increased
rate of lipid peroxidation in the absence Fe (II) in rat tissue homogenates especially at pH
5.4. This higher extent of lipid peroxidation can be explained by; the mobilized iron which
may come from reserves where it is weakly bound. Addition of iron (Fe) chelator
desferoxamine (DFO) to reaction medium completely inhibited the peroxidation processes
at all studied pH values including acidic values (5.8-5.4). In the presence of Fe (II) acidosis
also enhanced detrimental effect of Fe (II) especially at pH (6.4-5.4). All Tested
compounds significantly protected lipid peroxidation at all studied pH values, except
ebselen which offered only a small statistically non-significant protection. The highest antioxidant
potency was observed for diphenyl ditelluride. These differences in potencies were
explained by the mode of action of these compounds using their catalytic anti-oxidant
cycles. We have also tested the thiol oxidase activity of diphenyl ditelluride as thiol
oxidation by diphenyl ditelluride is a favorable reaction and may be responsible for
alteration in regulatory or signaling pathways. We have measured rate constants for
reactions of diphenyl ditelluride with cysteine, dimercaptosuccinic acid, glutathione and
dithiothreitol in phosphate buffer. The relative reactivities of the different thiols with
diphenyl ditelluride were independent of the pKa of the thiol group, such that at pH 7.4,
cysteine AND dithiothreitol were the most reactive and low reactivity was observed with
glutathione and dimercaptosuccinic acid. The reactivity of diphenyl ditelluride was not
modified by change in pH. Rate of oxidation increased with increasing pH for all thiols
except dimercaptosuccinic acid, where the rate of oxidation was faster at low pH. This
study provides in-vitro evidence for acidosis induced oxidative stress and in rat tissues and
potential anti-oxidant action of Our observations will be of importance in our understanding of pathologies which are
associated with low tissue pH. These studies confirm that organochalcogens are redox
active within physiologically relevant potential range. The implication from these results
for a biological system is that these compounds may react with thiols on the basis of their
chemical reactivity. If it is selective, accessibility or other molecular features may be more
important determinants. Furthermore other aspect that deserve investigation is to determine
a possible relationship between thiol-peroxidase activity of these compounds with the
capacity of catalyzing thiol/sulfide exchange, and how these two chemical properties of
selenide/tellurides correlates with their toxicological and pharmacological effects. | por |
dc.contributor.advisor1 | Rocha, João Batista Teixeira da | |
dc.contributor.advisor1Lattes | http://lattes.cnpq.br/3935055744673018 | por |
dc.contributor.referee1 | Santos, Jose Eduardo Tanus dos | |
dc.contributor.referee2 | Klamt, Fábio | |
dc.contributor.referee3 | Bem, Andreza Fabro de | |
dc.contributor.referee4 | Posser, Thais | |
dc.creator.Lattes | http://lattes.cnpq.br/0384454976208820 | por |
dc.publisher.country | Brasil | por |
dc.publisher.department | Bioquímica | por |
dc.publisher.initials | UFSM | por |
dc.publisher.program | Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica | por |
dc.subject.cnpq | CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA | por |
dc.publisher.unidade | Centro de Ciências Naturais e Exatas | por |