Protective effects of D-glucaro-1,4-lactone against oxidative modifications in blood platelets.
OBJECTIVE
Peroxynitrite (ONOO-), a highly reactive species, modulates platelet activation and function. Modifications of platelet proteins induced by ONOO- may be an important factor in the pathogenesis of platelet-related diseases. The defence mechanisms against ONOO- are therefore crucial for normal cellular function. Recently, there has been an increased interest in the screening of natural products present in the diet and herbals for possible antioxidative agents (ONOO( scavengers). D-glucaro-1,4-lactone (1,4-GL), formed from D-glucaric acid (GA), a natural compound found in fruits and vegetables, possesses detoxifying and anticancerogenic properties. However, the effect of this compound on platelet activation is unknown.


RESULTS
We investigated the effects of 1,4-GL on nitrative and oxidative alteration of platelet proteins and lipid peroxidation caused by two strong oxidants: ONOO- and hydroperoxide (H2O2). The action of 1,4-GL on platelet aggregation induced by adenosine diphosphate (ADP) was also studied. Exposure of platelets to ONOO- or H2O2 resulted in an increase in the level of carbonyl groups (approximately three-fold and two-fold, respectively). In the presence of 1,4-GL, a significant decrease (about 50% for the highest concentration of 1,4-GL) in carbonyl group formation was observed; however the level of nitrotyrosine residues in platelets treated with ONOO- remained unchanged.


CONCLUSIONS
We demonstrated an inhibitory effect of 1,4-GL on lipid peroxidation in platelets treated with ONOO- (0.1mM) or H2O2 (2mM). 1,4-GL inhibited platelet lipid peroxidation by about 40%. In the presence of 1,4-GL, peroxidation of plasma lipids was also reduced by about 40%. These results demonstrate that 1,4-GL possesses antioxidative properties and reduces the activation of blood platelets.
Saluk-Juszczak
Joanna
J
Department of General Biochemistry, Institute of Biochemistry, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland. juszczak@biol.uni.lodz.pl
Olas
Beata
B
Nowak
Paweł
P
Staroń
Agnieszka
A
Wachowicz
Barbara
B
D000704:Analysis of Variance; D019540:Area Under Curve; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017392:Thiobarbituric Acid Reactive Substances; D030421:Peroxynitrous Acid; C009194:saccharolactone; D006861:Hydrogen Peroxide; D005937:Glucaric Acid