RESUMEN

Humans have widespread exposure to both oxidants, and soft electrophilic compounds such as alpha,beta-unsaturated aldehydes and quinones. Electrophilic motifs are commonly found in a drugs, industrial chemicals, pollutants and are also generated via oxidant-mediated degradation of biomolecules including lipids (e.g. formation of 4-hydroxynonenal, 4-hydroxyhexenal, prostaglandin J2). All of these classes of compounds react efficiently with Cys residues, and the particularly the thiolate anion, with this resulting in Cys modification via either oxidation or adduct formation. This can result in deleterious or beneficial effects, that are either reversible (e.g. in cell signalling) or irreversible (damaging). For example, acrolein is a well-established toxin, whereas dimethylfumarate is used in the treatment of multiple sclerosis and psoriasis. This short review discusses the targets of alpha,beta-unsaturated aldehydes, and particularly two prototypic cases, acrolein and dimethylfumarate, and the factors that control the selectivity and kinetics of reaction of these species. Comparison is made between the reactivity of oxidants versus soft electrophiles. These rate constants indicate that electrophiles can be significant thiol modifying agents in some situations, as they have rate constants similar to or greater than species such as H2O2, can be present at higher concentrations, and are less efficiently removed by protective systems when compared to H2O2. They may also induce similar or higher levels of modification than highly reactive oxidants, due to the very low concentrations of oxidants formed in most in vivo situations.

Asunto(s)

Cisteína , Oxidantes , Acroleína , Aldehídos/química , Cisteína/química , Dimetilfumarato , Humanos , Peróxido de Hidrógeno , Cinética

RESUMEN

Although widely consumed, dietary supplements based on Vitamin C contain high doses of this compound, whose impact on lipid oxidation during digestion needs to be addressed. Therefore, the effect of seven commercial supplements and of pure l-ascorbic acid and ascorbyl palmitate on linseed oil during in vitro gastrointestinal digestion was tackled. The advance of lipid oxidation was studied through the generation of oxidation compounds, the degradation of polyunsaturated fatty acyl chains and of gamma-tocopherol, by employing Proton Nuclear Magnetic Resonance. Supplements containing exclusively l-ascorbic acid enhanced the advance of linseed oil oxidation during digestion. This was evidenced by increased formation of linolenic-derived conjugated hydroxy-dienes and alkanals and by the generation of conjugated keto-dienes and reactive alpha,beta-unsaturated aldehydes, such as 4,5-epoxy-2-alkenals; moreover, gamma-tocopherol was completely degraded. Conversely, supplements composed of mixtures of ascorbic acid/salt with citric acid and carotenes, and of ascorbyl palmitate, protected linseed oil against oxidation and reduced gamma-tocopherol degradation. The study through Solid Phase Microextraction-Gas Chromatography/Mass Spectrometry of the volatile compounds of the digests corroborated these findings. Furthermore, a decreased lipid bioaccessibility was noticed in the presence of the highest dose of l-ascorbic acid. Both the chemical form of Vitamin C and the presence of other ingredients in dietary supplements have shown to be of great relevance regarding oxidation and hydrolysis reactions occurring during lipid digestion.