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Biomedical subjects

Lluís Arola

Publications and source records attributed to Lluís Arola.

10 recordsLinked to original sources

Tetramethylated dimeric procyanidins are detected in rat plasma and liver early after oral administration of synthetic oligomeric procyanidins.

Procyanidins (PC) are of great interest in nutrition because they account for a major fraction of the total flavonoids ingested in Western diets and have health benefits in humans. However, it remains unknown which species of PC, namely, monomers, oligomers, or aromatic acid derivatives of gut microflora, are responsible for their beneficial effects in vivo. The high molecular complexity of PC extracts and PC-rich foods is a major problem in absorption studies. To circumvent this difficulty, we have synthesized oligomeric PC consisting of (-)-epicatechin units linked by ethyl bridges. The synthetic PC (SPC) only contains dimers, trimers, tetramers, and nanomers. After oral gavage of this SPC (200 mg/kg body weight) to male Wistar rats, tetramethylated dimeric PC (TDPC) were detected in plasma and liver. TDPC were detected in plasma as soon as 1 h after intake, reaching maximum concentrations (14 mg/L) 2 h after gavage. At this time, liver contained as much as 15 mug of TDPC per gram of tissue. In conclusion, orally administered dimeric PC are rapidly absorbed and internally methylated in rats. To our knowledge, this is the first time that methylated dimeric PC have been detected in plasma and liver. We consider that plasma and liver concentrations of TDPC are sufficient to exert a hormone-like effect and, therefore, that PC dimers are good candidates as agents of the biological activities of PC extracts and PC-rich foods.

Absorption↗

Procyanidin effects on adipocyte-related pathologies.

Procyanidins, a class of flavonoids, have clear and well-defined beneficial effects against several pathologies including cardiovascular heart disease. Now, studies in vivo are revealing the effects of procyanidins against obesity, where they prevent weight gain and adipose tissue mass increase, and against diabetes and insulin resistance, where they act as antihiperglycemic agents. Several mechanisms may be responsible for these effects. One of these, due to the key role of adipose tissue in the development of obesity and insulin resistance, is their effect on adipocytes. In this review we compile the studies that indicate a protective role for procyanidins in obesity and insulin resistance, focusing on their effects on the adipocyte, where procyanidins modify lipid synthesis, lipid degradation, glucose uptake, and adipose differentiation.

Adipocytes↗

Moderate red-wine consumption partially prevents body weight gain in rats fed a hyperlipidic diet.

Red wine is a beverage that can exert a broad spectrum of health-promoting actions both in humans and laboratory animal models if consumed moderately. However, information about its effect on body weight is scarce. We have evaluated the effect of moderate red wine consumption on body weight and energy intake in male Zucker lean rats fed a hypercaloric diet for 8 weeks. For this purpose, we used three 5-animal groups: a high-fat diet group (HFD), a high-fat-diet red-wine-drinking group (HFRWD), and a standard diet group (SD). After 8 weeks, the HFRWD group had a lower body weight gain (175.66 +/- 2.78% vs 188.22 +/- 4.83%; P<.05) and lower energy intake (269.45 +/- 4.02 KJ/animal.day vs day vs 300.81 +/- 4.52 KJ/animal.day; P<.05) and had less fat mass at epididymal location respect to the whole body weight (0.014 +/- 0.001 vs 0.017 +/- 0.001; P<.05) than the HFD group. However, the red wine didn't modified the fed efficiency 0.012 +/- 0.001 g/KJ for HFRWD group versus 0.013 +/- 0.001 g/KJ for the HFD one (P=.080). These findings, though preliminary, show that moderate red wine intake can prevent the increase of body weight by modulating energy intake in a rat diet-induced model of obesity.

Adiposity↗

Grape seed procyanidins prevent oxidative injury by modulating the expression of antioxidant enzyme systems.

In the present paper, we report the effect of a grape seed procyanidin extract (GSPE) on antioxidant enzyme systems (AOEs). Gene expression was tested using the hepatocarcinoma cell line HepG2 by exposing it to several GSPE doses between 0 and 100 mg/L for 24 h. We evaluated mRNA expression and enzyme activity levels using real time RT-PCR and spectrophotometry. The results suggested a transcriptional GSPE regulation of glutathione related enzymes caused by an increase both in mRNA and in enzyme activity levels overall at 15 mg/L. We also assessed the GSPE effect on AOEs in cells submitted to oxidative stress. Under oxidative conditions (1 mM H(2)O(2), 1 h), we found a decrease in GSH content and an increase in MDA, and we suggested a posttranslational regulation of GPx/GR mRNAs and a transcriptional enhancement of GST mRNA. The GSPE pretreatment (15 mg/L, 23 h) before HepG2 submission to H(2)O(2) (1 mM, 1 h) showed an increase of the mRNA of GPx/GR with respect to the H(2)O(2) group, whereas the GSH content was similar to the control group. However, the GPx/GR enzyme activities were not increased. We hypothesize that GSPE probably improves the cellular redox status via glutathione synthesis pathways instead of regulation of the GPx and/or GR activities protecting against oxidative damage.

Cell Line, Tumor↗

Intracellular mediators of procyanidin-induced lipolysis in 3T3-L1 adipocytes.

We have previously reported that grape seed procyanidins stimulate long-term lipolysis on 3T3-L1 fully differentiated adipocytes. To unravel the molecular mechanism by which procyanidins exert this effect, we checked the involvement of two main cellular targets in adipose cells: protein kinase A (PKA) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Procyanidin treatment increased intracellular cAMP levels in 3T3-L1 adipocytes, and their lipolytic effect was inhibited by simultaneous treatment with H89, a PKA specific inhibitor. BRL49653, a very highly specific ligand of PPAR-gamma, totally abolished the lipolytic effect of procyanidins. Simultaneous to this long-term lipolytic effect, the mRNA levels of some differentiation adipocyte markers decreased, although there were no changes in the triglyceride content of the cells. BRL49653 did not antagonize the decrements of differentiation markers. These results support a mediation of PPAR-gamma and PKA on the lipolytic effects of procyanidins on 3T3-L1 adipocytes.

3T3 Cells↗

Antigenotoxic effect of grape seed procyanidin extract in Fao cells submitted to oxidative stress.

The protective effects of grape seed procyanidin extract on the repair of H(2)O(2)-induced DNA lesions were tested using Fao cells. Cells were exposed to 600 microM H(2)O(2) for 3 or 21 h. A procyanidin extract from grape seed (PE) was incubated or preincubated (1 h) during the exposure to H(2)O(2). The ability of procyanidins to protect against the genotoxicity of H(2)O(2) was compared with those of the monomeric flavanols (+)-catechin and (-)-epicatechin and the flavonol quercetin. After treatment, DNA damage was monitored using alkaline single-cell gel electrophoresis (the comet assay) (Aherne, S. A.; O'Brien, N. M. Nutr. Cancer 1999, 34, 160-166). At the end of the experiment, PE significantly decreased the damage caused by H(2)O(2). The results also showed that quercetin was the most effective of the flavonoids tested, which is consistent with its powerful antioxidant character. The results indicate that procyanidins are more effective than the corresponding individual monomers, catechin and epicatechin, at preventing DNA lesions in hepatocytes and that this protection is higher after preincubation than after co-incubation.

Antimutagenic Agents↗

New method for evaluating astringency in red wine.

Astringency is an important sensory attribute of red wine. It is usually estimated by tasting and is subject to a certain subjectivity. It can also be estimated by using the gelatin index. This procedure is not very reproducible because there are many gelatins on the market with a heterogeneous composition. Furthermore, the gelatin index determines procyanidin concentration by acid hydrolysis that gives only an approximate result. This paper proposes a new and reproducible method that determines astringency by using ovalbumin as the precipitation agent and tannic acid solutions as standards. Statistical analysis of the results indicates that this method is more reproducible (RSD = 5%) than the gelatin index (RSD = 12%) and correlates better with sensorial analysis.

Chemical Precipitation↗

Frameshift mutation events in beta-glucosidases.

Compensated frameshift mutation is a modification of the reading frame of a gene that takes place by way of various molecular events. It appears to be a widespread event that is only observed when homologous amino acid and nucleodotide sequences are compared. To identify these mutation events, the sequence analysis rationale was based on the search for short regions that would have much lower degrees of conservation in protein, but not in DNA, in well-conserved beta-glucosidase families. We have restricted our study to a seed set of sequences of O-glycoside hydrolase families 1 and 3. We found compensated frameshift mutation in the family of 1 beta-glucosidases for the Erwinia herbicola, Cellulomonas fimi, and (non-cyanogenic) Trifolium repens gene sequences, and in the family of 3 beta-glucosidases for the Clostridium thermocellum and Clostridium stercorarium gene sequences. By computational treatment, the observed mutation events in the gene frameshifting sub-sequence have been neutralised. Each nucleotide insertion must be eliminated and each nucleotide deletion must be substituted by the symbol N (any nucleotide). When the frameshifting fragments of the amino acid sequences were substituted by the computationally neutralised subsequences, the beta-glucosidase alignments were improved. We also discuss the structural implications of the compensated frameshift mutations events.

Amino Acid Sequence↗

Human apo A-I and rat transferrin are the principal plasma proteins that bind wine catechins.

The processes of absorption, blood transport, tissular distribution, metabolism, and excretion are at present understood very little. The aim of this study was to investigate blood transport and identify which principal plasma proteins in humans and rats bind to monomeric catechin and procyanidins in red wine ex vivo. Human and rat plasma and serum were incubated with (+)-catechin and procyanidins from grape seed, the origin of red wine catechins. Proteins were separated by SDS-PAGE and native-PAGE to determine which proteins bound to these compounds. The principal protein that bound to (+)-catechin in each species was sequenced. SDS-PAGE showed that (+)-catechin and procyanidins mainly bound to a protein of about 80 kDa in rats and 35 kDa in humans. Their sequencing indicated that these proteins were apo A-I in humans and transferrin in rats. The fact that red wine procyanidins bind to both proteins suggests that they may have a role in reverse cholesterol transport and in the oxidizing action of iron.

Adult↗

Simultaneous horizontal gene transfer of a gene coding for ribosomal protein l27 and operational genes in Arthrobacter sp.

Phylogenetic analysis of bacterial L27 ribosomal proteins showed that, against taxonomy, the L27 protein from the Actinobacteria Arthrobacter sp. clusters with protein sequences from the Bacillus group. The L27 gene clusters in the Arthrobacter sp. genome with six genes responsible for creatinine and sarcosine degradation. Phylogenetic analyses of orthologue proteins encoded by three of these genes also showed a phylogenetic relationship with Bacillus species. Comparisons between the synonymous codon usage of the Arthrobacter sp. genes and those from complete genomes showed that Arthrobacter genes encoding the L27 ribosomal protein and the proteins responsible for the degradation of creatinine and sarcosine have a codon usage that is more similar to that of Bacillus species than that of Arthrobacter. We suggest that the Arthrobacter sp. genes encoding the L27 ribosomal protein and the proteins responsible for the degradation of creatinine and sarcosine were acquired simultaneously through horizontal gene transfer from an unknown Bacillus species.

Amino Acid Sequence↗