Biomedical subjects

Josep Lluís Torres

Publications and source records attributed to Josep Lluís Torres.

10 recordsLinked to original sources

PubMed2006

Inhibition of hemoglobin- and iron-promoted oxidation in fish microsomes by natural phenolics.

Natural phenolic antioxidants have been tested in hake (Merluccious merluccious) microsomes as inhibitors of lipid oxidation promoted by fish muscle prooxidants: hemoglobin (Hb), enzymatic NADH-iron and nonenzymatic ascorbate-iron. The phenolics selected were as follows: (a) a grape phenolic extract (OW), (b) a fraction (IV) with isolated grape procyanidins with a medium-low degree of polymerization and galloylation percentage, (c) hydroxytyrosol obtained from olive oil byproducts, and (d) a synthetic phenolic antioxidant, propyl gallate. All compounds delayed lipid oxidation activated by Hb, enzymatic NADH-iron, and nonenzymatic ascorbate-iron, excluding hydroxytyrosol that was not an effective antioxidant on oxidation promoted by nonenzymatic iron. The relative antioxidant efficiency was independent of the prooxidant system, IV > propyl gallate > OW > hydroxytyrosol, and showed a positive correlation with their incorporation into microsomes (p < 0.05). The reducing capacity or ability for donating electrons and the chelating properties may also contribute to the antioxidant activity of phenolics, although these factors were less decisive than their affinity for incorporating into the microsomes. Conversely, the inhibition of Hb oxidation by phenolics and their polarity did not seem to play an important role on antioxidant mechanism. These results stressed the importance of incorporating the exogenous antioxidants into the membranes where are located key substances for fish lipid oxidation (highly unsaturated phospholipids, iron-reducing enzymes, and endogenous alpha-tocopherol).

Animals↗

PubMed2006

Electron-transfer capacity of catechin derivatives and influence on the cell cycle and apoptosis in HT29 cells.

Galloylated and nongalloylated catechin conjugates with cysteine derivatives have been synthesized and evaluated for their capacity to scavenge free radicals and to influence crucial functions (cell cycle, apoptosis) in HT29 colon carcinoma cells. We show that the nonphenolic part of the molecule modified the capacity of catechins to donate hydrogen atoms and to transfer electrons to free radicals. Nongalloylated derivatives did not significantly influence either the cell cycle or apoptosis. Among the galloylated species, 4beta-[S-(O-ethyl-cysteinyl)]epicatechin 3-O-gallate, which showed a high electron-transfer capacity (5 e- per molecule), arrested the cell cycle and induced apoptosis as expected for galloylated catechins such as tea (-)-epigallocatechin 3-O-gallate. 4beta-[S-(N-Acetyl-O-methyl-cysteinyl)]epicatechin 3-O-gallate, which showed the highest hydrogen-donating capacity (10 H per molecule) while keeping the electron-transfer capacity low (2.9 e- per molecule), did not trigger any significant apoptosis. The gallate moiety did not appear to be sufficient for the pro-apoptotic effect of the catechin derivatives in HT29 cells. Instead, a high electron-transfer capacity is more likely to be behind this effect. The use of stable radicals sensitive exclusively to electron transfer may help to design molecules with either preventive scavenging action (high hydrogen donation, low electron transfer) or therapeutic pro-apoptotic activity (high electron transfer).

Apoptosis↗

PubMed2005

Efficient preparation of catechin thio conjugates by one step extraction/depolymerization of pine (Pinus pinaster) bark procyanidins.

The skin penetrating antioxidant cysteamine derivative of (-)-epicatechin as well as other thio conjugates were efficiently obtained with high yields from pine (Pinus pinaster) bark by simultaneous one pot extraction and depolymerization using water and cysteamine hydrochloride. The influence of the concentration of bark, acid, and cysteamine, as well as the reaction time on the total conversion, was studied. The total conversion into the epicatechin and catechin conjugates was as high as 47 g/kg pine bark with 1666 g cysteamine/kg bark and 28 g/kg with 166 g cysteamine/kg bark. A fast cleanup step by absorption/desorption on XAD-16 greatly facilitated further purification of the active major component. At a pilot scale, 4beta-(2-aminoethylthio)epicatechin (1) (conversion 263 g, purity 35% by reversed phase high-performance liquid chromatography/weight) was obtained from 17 kg of pine bark after simultaneous extraction/depolymerization followed by cleanup with the polymeric resin in approximately 10 h. The results show that pine (P. pinaster) bark is a suitable source of flavanols for the preparation of active thio derivatives. Conditions are given for the fast and efficient preparation of the conjugates.

Catechin↗

PubMed2005

Effect of new antioxidant cysteinyl-flavanol conjugates on skin cancer cells.

Novel catechin derivatives obtained from grape procyanidins and l-cysteine scavenge free radicals by hydrogen atom donation, rather than electron transfer, and reduce cell viability in A375 and M21 melanoma cells. In particular, 4beta-(S-cysteinyl)epicatechin 3-O-gallate has a free radical scavenging capacity as strong as that of tea (-)-epigallocatechin gallate and causes a significant S-phase cell-cycle arrest in both cell lines at doses higher than 100 microM. The other cysteinyl compounds do not affect normal cell cycle distribution. The gallate derivative also induces apoptosis in melanoma cells more strongly than the other derivatives and the parent (-)-epicatechin do. The gallate compound seems to trigger nuclear condensation and fragmentation, which is confirmed by DNA laddering. Interestingly, they do not induce apoptosis in keratinocytes (HaCaT).

Antineoplastic Agents, Phytogenic↗

PubMed2005

Procyanidin fractions from pine (Pinus pinaster) bark: radical scavenging power in solution, antioxidant activity in emulsion, and antiproliferative effect in melanoma cells.

Pine (Pinus pinaster) bark is a rich source of procyanidin oligomers. From a total polyphenolic extract, we have generated fractions of different procyanidin composition. The mixtures, devoid of gallate esters, were active as free radical scavengers against ABTS(*+), DPPH, and HNTTM. Pine bark fractions were tested for antioxidant activity in solution (hydrogen donation and electron transfer) and emulsion (inhibition of lipid peroxidation) and compared with their galloylated counterparts from grape origin. While galloylation clearly influenced the free radical scavenging efficiency in solution, it did not seem to play a determinant role in protection against lipid peroxidation in emulsion. The fractions were very mild inhibitors of cell proliferation. Because gallate esters appear to interfere with crucial cell functions, gallate free pine procyanidins may be the innocuous chemopreventative agents of choice for many applications in food and skin protection.

Antioxidants↗

PubMed2004

Reducing activity of polyphenols with stable radicals of the TTM series. Electron transfer versus H-abstraction reactions in flavan-3-ols.

A new method to test the antioxidant activity of polyphenols by electron transfer reactions to a stable organic free radical, tris(2,4,6-trichloro-3,5-dinitrophenyl)methyl radical (HNTTM), is reported. Therefore, the activity of the natural flavanols, (-)-epicatechin, and two synthetic derivatives, 4beta-(S-cysteinyl)epicatechin and 4beta-(2-aminoethylthio)epicatechin, can be differentiated by their capacity to transfer hydrogen atoms to 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and to transfer electrons to HNTTM. [structure: see text]

Journal Article↗

PubMed2004

Novel epicatechin derivatives with antioxidant activity modulate interleukin-1beta release in lipopolysaccharide-stimulated human blood.

We examine the potential antioxidant activity and the immune function of new epicatechin conjugates obtained by depolymerization of grape polymeric flavanols in the presence of cysteamine or cysteine. When incubated with an erythrocyte suspension, flavanols protected the erythrocyte membrane from hemolysis induced by 2,2'-azo-bis(2-amidinopropane)dihydrochloride (AAPH), an azo free radical initiator. The inhibitory effect was concentration-dependent and the IC50 was 119.8 microM for epicatechin, and 74.9 and 89.4 microM for the cysteine and cysteamine derivatives, respectively. These compounds were tested for their antioxidant activity and their capacity to modulate interleukin-1beta (IL-1beta), which is currently considered to be the major cytokine factor influencing the acute phase of the inflammatory response. At concentrations up to 20 microM, epicatechin and its derivatives inhibited the production of IL-1beta in whole blood incubated in the presence of E. coli lipopolysaccharide (LPS), in a concentration-dependent manner. The most active compound was the cysteamine derivative.

Antioxidants↗

PubMed2004

Efficient one pot extraction and depolymerization of grape (Vitis vinifera) pomace procyanidins for the preparation of antioxidant thio-conjugates.

Antioxidant thio-conjugates were obtained from white grape pomace by a clean and efficient one pot extraction and depolymerization method using water and cysteamine hydrochloride. To evaluate the potential of grape pomaces of different origins as sources of proanthocyanidins and conjugates, we conducted varietal comparative studies of polyphenol content, antioxidant power, and procyanidin composition. Xarel.lo proved to be the richest source of polyphenols. The total conversion into the conjugates was as high as 8 g/kg of Xarel.lo grape pomace, with a 50-fold excess of cysteamine, and 3 g/kg, with a 5-fold excess of cysteamine. After purification by preparative cation exchange and reversed phase high-performance liquid chromatography, 17 g of 63% pure 4beta-(2-aminoethylthio)epicatechin (acetate salt) was obtained from 35 kg of moist pomace. The procedure described here will make the antioxidant thio-derivatives efficiently available directly from raw plant byproducts such as grape pomace.

Antioxidants↗

PubMed2003

Mixed micellar electrokinetic capillary chromatography separation of depolymerized grape procyanidins.

Oligomeric procyanidins are potent antioxidant polyphenols of potential interest as disease-preventing agents. Their efficiency depends on the size and composition of their oligomeric structures. The mean degree of polymerization of these compounds is usually estimated by thiolysis with thiol-alpha-toluene followed by analysis using high-performance liquid chromatography (HPLC). We show the development of a mixed micellar electrokinetic chromatography (MEKC) method for the separation of the major components obtained after thiolysis with cysteamine (catechins and their cysteamine conjugates). MEKC studies using sodium dodecyl sulfate (SDS as pseudostationary phase led to long migration times, e.g., with 100 mM SDS, at pH 7, the solutes were separated in about 40 min), while the use of sodium cholate (SC) produced an elution window relatively short. Using a mixed micellar SC-SDS system (50 mM phosphate at pH 7 containing 40 mM SC and 10 mM SDS), it is possible to separate these compounds in less than 15 min. The proposed method is useful to separate the major components of the thiolysate in effluents from food processing (e.g., skins and seeds from grape and apple) considered as potential procyanidin sources.

Biflavonoids↗

PubMed2002

Valorization of grape (Vitis vinifera) byproducts. Antioxidant and biological properties of polyphenolic fractions differing in procyanidin composition and flavonol content.

Many byproducts and wastes generated by agroindustries contain polyphenols with potential application as food antioxidants and preventive agents against skin cancer and other diseases. The performance of polyphenolic fractions from Parellada grape (Vitis vinifera) pomace as antioxidants in different physicochemical environments was tested. Fractions containing oligomers with mean degree of polymerization between 3 and 4 and percentage galloylation ca. 30% were the most potent free radical scavengers and efficient antioxidants in an oil-in-water emulsion. A fraction including glycosylated flavonols was also efficient in the emulsion. All the fractions showed low aquatic toxicity and weak influence on proliferation of human melanoma cells.

Antioxidants↗