Jean-Max Rouanet

The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats

Rats were fed a grape seed extract (GSE) containing (+)-catechin, (-)-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a 24 h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to a greater extent the ileum 1 h after ingestion, and into the caecum after 2 h with relatively small amounts being detected in the colon after 3 h. The GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols. Plasma contained exclusively catechin glucuronides and methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B1, B2, B3 and B4 as well as the trimer C2 and an unknown GSE trimer. The amounts of (+)-catechin and (-)-epicatechin metabolites excreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding (-)-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidin oligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.

Chardonnay grape seed procyanidin extract supplementation prevents high-fat diet-induced obesity in hamsters by improving adipokine imbalance and oxidative stress markers.

Studies reported the effects of polyphenols but not for grape polyphenols towards obesity. We analysed the effects of a polyphenolic grape seed extract (GSE) on obesity and oxidative stress in hamsters receiving a high-fat diet (HFD). Three groups of hamsters received a standard diet (STD), or a HFD plus a daily gavage with water (Control, HFD) or a solution of GSE (HFD + GSE) for 12 wk. Plasma glucose, triglycerides (TG), insulin, leptin and adiponectin were measured. Oxidative stress was assessed by cardiac production of superoxide anion and NAD(P)H oxidase expression. After 12 wk, HFD increased abdominal fat as compared with standards. GSE avoided this feature. HFD led to higher plasma glucose, TG, insulin and greater insulin resistance (HOMA-IR) values. GSE prevented in part these effects, reducing insulinemia and leptinemia by 16.5 and 45%, respectively, whereas adiponectin level increased by 61% compared with obese controls. GSE lowered glycemia and HOMA-IR and strongly prevented cardiac production of superoxide by 74% and NAD(P)H oxidase expression by 30%. This is the first time that chronic consumption of grape phenolics is shown to reduce obesity development and related metabolic pathways including adipokine secretion and oxidative stress.

Silver nanoparticles: Their potential toxic effects after oral exposure and underlying mechanisms – A review

Because of their antimicrobial properties, the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, and medicine. In the food industry, nanoparticles are used in packaging to enable better conservation products such as sensors to track their lifetime, and as food additives, such as anti-caking agents and clarifying agents for fruit juices. Nanoemulsions, used to encapsulate, protect and deliver additives are also actively developed. Nanomaterials in foods will be ingested and passed through the digestive tract. Those incorporated in food packaging may also be released unintentionally into food, ending up in the gastrointestinal tract. It is therefore important to make a risk assessment of nanomaterials to the consumer. Thus, exposure to AgNPs is increasing in quantity and it is imperative to know their adverse effects in man. However, controversies still remain with respect to their toxic effects and their mechanisms. Understanding the toxic effects and the interactions of AgNPs with biological systems is necessary to handle these nanoparticles and their use. They usually generate reactive oxygen species resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signalling pathways. Here, we mainly focus on the routes of exposure of AgNPs, toxic effects and the mechanisms underlying the induced toxicity.

Polymeric grape seed tannins prevent plasma cholesterol changes in high-cholesterol-fed rats

Abstract The objective of this study was to determine the effect of grape seed tannins in either monomeric or polymeric form on plasma cholesterol in rats. These tannins were supplemented at a level of 2% of the diet of high-cholesterol-fed Sprague Dawley rats for 9 weeks; the diets were compared with a diet without tannins (control diet) and with a standard diet. Rats fed diets containing 1% cholesterol showed an increase in total and low-density lipoprotein plasma cholesterol and a decrease in plasma high-density lipoprotein. These changes were prevented by the addition of 2% polymeric grape tannins but not by monomeric tannins. Similarly, liver weight, liver lipids and total liver cholesterol were increased by dietary cholesterol and these increases were largely inhibited by the tannin polymers but not the monomers. The polymers significantly increased the faecal excretion of lipids and cholesterol. In conclusion, we have shown that polymeric grape seed tannins exert a hypocholesterolaemic effect in high-cholesterol-fed rats.

Superoxide Dismutase Administration, A Potential Therapy Against Oxidative Stress Related Diseases: Several Routes of Supplementation and Proposal of an Original Mechanism of Action

ABSTRACTOxidative stress, involved in many diseases, is defined as an impaired balance between reactive oxygen species (ROS) production and antioxidant defences. Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in diminishing oxidative stress. Thus, the removal of ROS by exogenous SODs could be an effective preventive strategy against various diseases. The poor bioavailability of exogenous SODs has been criticized. However, improvements in SOD formulation may overcome this limitation and boost interest in its therapeutic properties. Here, we provide a review of animal and human studies about SODs supplementation in order to evaluate their therapeutic value. Protective effects have been observed against irradiation, carcinogenesis, apoptosis and neurodegeneration. SODs administration has also been reported to alleviate inflammatory, infectious, respiratory, metabolic and cardiovascular diseases and genitourinary and fertility disorders, raising the question of its mechanism of action in these diverse situations. Some authors have shown an increase in endogenous antioxidant enzymes after exogenous SODs administration. The induction of endogenous antioxidant defence and, consequently, a decrease in oxidative stress, could explain all the effects observed. Further investigations need to be carried out to test the hypothesis that SODs supplementation acts by inducing an endogenous antioxidant defence.

Antioxidant effects of dietary polymeric grape seed tannins in tissues of rats fed a high cholesterol-vitamin E-deficient diet

Effects of dietary monomeric and polymeric grape seed tannins on the activity of antioxidant enzymes, total glutathione and level of lipid peroxidation in various tissues were investigated in rats fed a high cholesterol diet poor in vitamin E. They were compared with those in rats receiving a high cholesterol-vitamin E-sufficient diet without addition of tannins. Four groups of rats were studied for 10 weeks: Group 1, sufficient vitamin E diet; Group 2, deficient vitamin E diet; Group 3, deficient vitamin E diet + monomeric tannins (71 mg/kg); Group 4, deficient vitamin E diet + polymeric tannins (71 mg/kg). Compared with a normal vitamin E diet (Group 1), aortic, cardiac, hepatic, intestinal, muscular and renal catalase, glutathione peroxidase and superoxide dismutase activities were significantly lower in rats receiving the deficient vitamin E diet (Group 2); polymeric tannins (Group 4), but not monomeric tannins, were able to restore all these enzymic activities. In all tissues and in blood, total glutathione concentration, which was significantly lowered by vitamin E deficiency, was brought to the normal level only with polymeric tannins. Furthermore, the lipid peroxidation in plasma and tissues was significantly reduced in the presence of supplemented polymeric tannins as much as in the presence of vitamin E. It is therefore likely that polymeric grape seed tannins function as antioxidants in vivo, negating the effects of the oxidative stress induced by both vitamin E deficiency and atherogenic diet.

Phenolics from purple grape, apple, purple grape juice and apple juice prevent early atherosclerosis induced by an atherogenic diet in hamsters.

Knowledge of the effects of processing on the antioxidant properties of fruits is limited. We investigated the processing of apple (A) and purple grape (PG) and their juices (AJ and PGJ) in hypercholesterolemic hamsters. Five groups of eight hamsters each were fed an atherogenic diet for 12 wk. They received daily by gavage either 7.14 mL/(kg x day) of mashed A or PG, or the same volume of AJ or PGJ, or water as control. Plasma cholesterol, non-HDL cholesterol, liver superoxide dismutase and glutathione peroxidase activities, and thiobarbituric acid reactive substances were efficiently reduced by the fruits and their juices compared with controls, whereas plasma antioxidant capacity was increased and aortic fatty streak area was decreased from 48 to 93%. For each of these parameters, the efficacy was PGJ > PG > AJ > A. The results show for the first time that long-term consumption of antioxidants supplied by apple and purple grape, especially phenolic compounds, prevents the development of atherosclerosis in hamsters, and that processing can have a major impact on the potential health benefits of a product. The underlying mechanism is related mainly to increased antioxidant status and improved serum lipid profile.

Dietary exposure to silver nanoparticles in Sprague–Dawley rats: Effects on oxidative stress and inflammation

Due to undesirable hazardous interactions with biological systems, we evaluated the effect of silver nanoparticles (AgNPs) intake on oxidative stress and inflammation. Rats received for 81 days a standard diet (Controls) or a standard diet plus 500 mg/d/kg BW AgNPs. We assayed plasma lipids, and oxidative stress was assessed by measuring liver and heart superoxide anion production (O₂°⁻) and liver malondialdehyde levels (MDA). Antioxidant status was appraised using plasma paraoxonase activity (PON), plasma antioxidant capacity (PAC) and liver superoxide dismutase activity (SOD). Liver inflammatory cytokines TNFα and IL-6 levels and plasma alanine aminotransferase (ALT) were assayed. Compared with Controls, AgNPs raised cholesterolemia (9.5%), LDL-cholesterol (30%), and lowered triglycerides (41%). They also increased liver (30%) and cardiac (41%) O₂°⁻ production, reduced PON activity (15%) and raised liver TNFα (9%) and IL-6 (∼12%). Plasma ALT activity rose (12%) after treatment with AgNPs. However, PAC and liver MDA and SOD activity were unchanged. These features indicate that exposure to 500 mg/d/kg BW of AgNPs results in liver damage by a dysregulation of lipid metabolism, highlighting liver and heart as the most sensitive organs to the deleterious effects. Our findings also demonstrate for the first time the oxidative and inflammatory effects of dietary AgNPs.

Hydrogen Peroxide Generation in Caco-2 Cell Culture Medium by Addition of Phenolic Compounds: Effect of Ascorbic Acid

Phenolic compounds have recently attracted special attention due to their beneficial health effects; their intestinal absorption and bioavailability need, therefore, to be investigated and Caco-2 cell culture model appeared as a promising tool. We have shown herein that the addition of a grape seed extract (GSE) to Dulbeccos modified Eagles medium (DMEM) used for Caco-2 cell culture leads to a substantial loss of catechin, epicatechin and B2 and B3 dimers from GSE in the medium after 24 h and to a production of hydrogen peroxide (H2O2). When 1420 microM ascorbic acid is added to the DMEM, such H2O2 production was prevented. This hydrogen peroxide generation substantially involves inorganic salts from the DMEM. We recommend that ascorbic acid be added to circumvent such a risk.

Effects of dietary grape seed tannins on rat cecal fermentation and colonic bacterial enzymes

Abstract In rats, the effects of a 12-wk supplementation of a purified diet with 71 mg/kg monomeric or polymeric grape seed tannins were explored on cecal fermentation and colonic bacterial enzymes. Weight gain was affected by addition of polymers to the diet. There was a significant increment of volatile fatty acids (VFA) pool and a pH decrease in the cecal contents of rats fed polymeric tannins, compared to controls. When expressed per gram of nitrogen content, the concentrations of all colonic fecal bacterial enzyme activities tested (β-glucosidase, β-glucuronidase, mucinase and nitroreductase) were decreased, due to a dilution effect. In these experimental conditions, monomeric tannins exhibited neither beneficial nor detrimental effect. On the other hand, these results show that although at a low dietary level equivalent of a daily amount of 0.5 L red wine, polymeric grape seed tannins exert a beneficial cecal metabolic and colonic protective effect.