Oximes as inhibitors of low density lipoprotein oxidation.
OBJECTIVE
Several lines of evidence support the hypothesis that the oxidation of low density lipoprotein (LDL) may play a crucial role in the initiation and progression of atherosclerosis. Various studies have shown a positive effect of antioxidant compounds on oxidative modification of LDL and atherogenesis. In view of this, we have investigated the possible antioxidant activity of two new oximes against Cu2+- induced LDL and serum oxidation. Oximes are used in organophosphate (OP) poisoning acting by restoring the cholinesterase function. However, their antioxidant capacities are not well understood and poorly studied.


METHODS
We measured, in a Cu2+-induced oxidation, the conjugated dienes formation in serum and LDL and the loss of tryptophan fluorescence as well as the TBARS formation in the LDL.


RESULTS
Our results showed that both oximes act as antioxidant and they are able to prevent LDL oxidation in a concentration-dependent manner. When human LDL or serum was oxidized by Cu2+, our oximes showed a significant increase in the lag phase of conjugated dienes and a significant decrease in the thiobarbituric acid reactive substances production. Moreover, oximes protected tryptophan residues of ApoB-100 in the early stage of LDL oxidation and during the subsequent propagation phase.


CONCLUSIONS
These results indicated for the first time that oximes have a potential antioxidant activity and they could act in the prevention of LDL and serum oxidation. Thus, we speculated that our oximes could act as antiatherogenic compounds besides their well described role as antidote for organophosphate poisoning.
de Lima Portella
Rafael
R
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS, Brazil.
Barcelos
Rômulo Pillon
RP
de Bem
Andreza Fabro
AF
Carratu
Vanessa Santana
VS
Bresolin
Leandro
L
da Rocha
João Batista Teixeira
JB
Soares
Félix Alexandre Antunes
FA
D019327:Copper Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D015394:Molecular Structure; D062025:Organophosphate Poisoning; D010084:Oxidation-Reduction; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D011041:Poisoning / Q000097:blood / Q000188:drug therapy; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008077:Lipoproteins, LDL; D010091:Oximes; D017392:Thiobarbituric Acid Reactive Substances; D019327:Copper Sulfate