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The application of stilbenes in the food industry is being considered because of their biological activities. Piceatannol, pterostilbene and ε-viniferin have awakened the industry’s interest. However, before they can be commercialized, we must first guarantee their safety for consumers. The present work reviews the toxicological studies performed with these stilbenes. A wide variety of studies has demonstrated their cytotoxic effects in both cancer and non-cancerous cell lines. In contrast, although DNA damage was detected by some authors, in vitro genotoxic studies on the effects of piceatannol, pterostilbene, and ε-viniferin remain scarce. None of the three reviewed substances have been evaluated using the in vitro tests required by the European Food Safety Authority (EFSA) as the first step in genotoxicity testing. We did not find any study on the toxic effects of these stilbenes in vivo. Thus, more studies are needed to confirm their safe use before they can be authorized as additive in the food industry.
Concepción Medrano-Padial; Ana Prieto; María Puerto; Silvia Pichardo. Toxicological Evaluation of Piceatannol, Pterostilbene, and ε-Viniferin for Their Potential Use in the Food Industry: A Review. Foods 2021, 10, 592 .
AMA StyleConcepción Medrano-Padial, Ana Prieto, María Puerto, Silvia Pichardo. Toxicological Evaluation of Piceatannol, Pterostilbene, and ε-Viniferin for Their Potential Use in the Food Industry: A Review. Foods. 2021; 10 (3):592.
Chicago/Turabian StyleConcepción Medrano-Padial; Ana Prieto; María Puerto; Silvia Pichardo. 2021. "Toxicological Evaluation of Piceatannol, Pterostilbene, and ε-Viniferin for Their Potential Use in the Food Industry: A Review." Foods 10, no. 3: 592.
Sulfur dioxide is a controversial preservative used in winemaking. Given its potential toxicity, it is of great interest to find alternatives aimed at replacing or reducing sulfur dioxide. The objective was to assess the antioxidant effects of a grapevine-shoot extract with 99% of stilbenes (ST-99), its major compounds (trans-resveratrol and trans-ε-viniferin) and their mixture (1:3.9) by measuring reactive oxygen species (ROS) and glutathione (GSH) levels in vitro. Their ability to protect against or reverse the effects of H2O2 on cells were also studied. The results showed that ST-99, followed by trans-ε-viniferin and the mixture, were able to reduce ROS levels, increased GSH content and exhibited antioxidant ability against an induced oxidative stress. Trans-resveratrol significantly reduced ROS content only at the highest concentrations. ST-99 at non-cytotoxic concentrations is more effective than the other compounds, which might be attributed to increased levels of GSH. The results suggest a promising use of ST-99.
Concepción Medrano-Padial; María Puerto; Tristan Richard; Emma Cantos-Villar; Silvia Pichardo. Protection and reversion role of a pure stilbene extract from grapevine shoot and its major compounds against an induced oxidative stress. Journal of Functional Foods 2021, 79, 104393 .
AMA StyleConcepción Medrano-Padial, María Puerto, Tristan Richard, Emma Cantos-Villar, Silvia Pichardo. Protection and reversion role of a pure stilbene extract from grapevine shoot and its major compounds against an induced oxidative stress. Journal of Functional Foods. 2021; 79 ():104393.
Chicago/Turabian StyleConcepción Medrano-Padial; María Puerto; Tristan Richard; Emma Cantos-Villar; Silvia Pichardo. 2021. "Protection and reversion role of a pure stilbene extract from grapevine shoot and its major compounds against an induced oxidative stress." Journal of Functional Foods 79, no. : 104393.
Genotoxic data of substances that could be used as food additives are required by the European Food Safety Authority. In this sense, the use of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99), due to its antioxidant and antibacterial activities, has been proposed as an alternative to sulfur dioxide in wine. The aim of this work was to study, for the first time, the in vivo genotoxic effects produced in rats orally exposed to 90, 180, or 360 mg ST-99/kg body weight at 0, 24, and 45 h. The combination of micronucleus assay in bone marrow (OECD 474) and standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach, liver, and blood of exposed animals. The ST-99 revealed no in vivo genotoxicity. These results were corroborated by analytical studies that confirm the presence of stilbenes and their metabolites in plasma and tissues. Moreover, to complete these findings, a histopathological study was performed under light microscopy in liver and stomach showing only slight modifications in both organs at the highest concentration used. The present work confirms that this extract is not genotoxic presenting a good profile for its potential application as a preservative in the wine industry.
Concepción Medrano-Padial; María Puerto; Ana Isabel Prieto; Nahúm Ayala; Pauline Beaumont; Caroline Rouger; Stéphanie Krisa; Silvia Pichardo. In Vivo Genotoxicity Evaluation of a Stilbene Extract Prior to Its Use as a Natural Additive: A Combination of The Micronucleus Test and The Comet Assay. Foods 2021, 10, 439 .
AMA StyleConcepción Medrano-Padial, María Puerto, Ana Isabel Prieto, Nahúm Ayala, Pauline Beaumont, Caroline Rouger, Stéphanie Krisa, Silvia Pichardo. In Vivo Genotoxicity Evaluation of a Stilbene Extract Prior to Its Use as a Natural Additive: A Combination of The Micronucleus Test and The Comet Assay. Foods. 2021; 10 (2):439.
Chicago/Turabian StyleConcepción Medrano-Padial; María Puerto; Ana Isabel Prieto; Nahúm Ayala; Pauline Beaumont; Caroline Rouger; Stéphanie Krisa; Silvia Pichardo. 2021. "In Vivo Genotoxicity Evaluation of a Stilbene Extract Prior to Its Use as a Natural Additive: A Combination of The Micronucleus Test and The Comet Assay." Foods 10, no. 2: 439.
The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing the size of HIV reservoirs within the mesenteric lymphatic system.
Chaolong Qin; Yenju Chu; Wanshan Feng; Christophe Fromont; Sijia He; Joseph Ali; Jong Bong Lee; Atheer Zgair; Mattia Berton; Sara Bettonte; Ruiling Liu; Lei Yang; Teerapong Monmaturapoj; Concepción Medrano-Padial; Allen Alonso Rodríguez Ugalde; Daria Vetrugno; Shi Ying Ee; Charles Sheriston; Yuntao Wu; Michael J. Stocks; Peter M. Fischer; Pavel Gershkovich. Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach. Journal of Controlled Release 2020, 329, 1077 -1089.
AMA StyleChaolong Qin, Yenju Chu, Wanshan Feng, Christophe Fromont, Sijia He, Joseph Ali, Jong Bong Lee, Atheer Zgair, Mattia Berton, Sara Bettonte, Ruiling Liu, Lei Yang, Teerapong Monmaturapoj, Concepción Medrano-Padial, Allen Alonso Rodríguez Ugalde, Daria Vetrugno, Shi Ying Ee, Charles Sheriston, Yuntao Wu, Michael J. Stocks, Peter M. Fischer, Pavel Gershkovich. Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach. Journal of Controlled Release. 2020; 329 ():1077-1089.
Chicago/Turabian StyleChaolong Qin; Yenju Chu; Wanshan Feng; Christophe Fromont; Sijia He; Joseph Ali; Jong Bong Lee; Atheer Zgair; Mattia Berton; Sara Bettonte; Ruiling Liu; Lei Yang; Teerapong Monmaturapoj; Concepción Medrano-Padial; Allen Alonso Rodríguez Ugalde; Daria Vetrugno; Shi Ying Ee; Charles Sheriston; Yuntao Wu; Michael J. Stocks; Peter M. Fischer; Pavel Gershkovich. 2020. "Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach." Journal of Controlled Release 329, no. : 1077-1089.
The use of stilbenes has been proposed as an alternative to sulfur dioxide in wine. Provided the feasibility from a technological approach, the cytotoxicity of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99 extract) was assessed in the human cell lines HepG2 and Caco-2. In addition, the effects of the main stilbenes found in ST-99, trans-resveratrol and trans-ε-viniferin were studied, as well as its mixture. Similar cytotoxic effects were obtained in the exposures to trans-ε-viniferin, ST-99 and the mixture; however, trans-resveratrol alone exerted less toxicity. When HepG2 cells were exposed to trans-ε-viniferin, ST-99 and the mixture, the mean effective concentration (EC50) were 28.28 ± 2.15, 31.91 ± 1.55 and 29.47 ± 3.54 µg/mL, respectively. However, in the exposure to trans-resveratrol, the EC50 was higher 50µ/mL. The morphological study evidenced damage at ultrastructural level in HepG2 cells, highlighting the inhibition of cell proliferation and the induction of apoptosis. The type of interaction produced by trans-ε-viniferin and trans-resveratrol mixtures was assessed by an isobologram analysis using the CalcuSyn software, evidencing an antagonist effect. These data comprise a starting point in the toxicological assessment; further studies are needed in this field to assure the safety of the extract ST-99.
Concepción Medrano-Padial; María Puerto; María Del Mar Merchán-Gragero; Francisco Javier Moreno; Tristan Richard; Emma Cantos-Villar; Silvia Pichardo. Cytotoxicity studies of a stilbene extract and its main components intended to be used as preservative in the wine industry. Food Research International 2020, 137, 109738 .
AMA StyleConcepción Medrano-Padial, María Puerto, María Del Mar Merchán-Gragero, Francisco Javier Moreno, Tristan Richard, Emma Cantos-Villar, Silvia Pichardo. Cytotoxicity studies of a stilbene extract and its main components intended to be used as preservative in the wine industry. Food Research International. 2020; 137 ():109738.
Chicago/Turabian StyleConcepción Medrano-Padial; María Puerto; María Del Mar Merchán-Gragero; Francisco Javier Moreno; Tristan Richard; Emma Cantos-Villar; Silvia Pichardo. 2020. "Cytotoxicity studies of a stilbene extract and its main components intended to be used as preservative in the wine industry." Food Research International 137, no. : 109738.
Cylindrospermopsin (CYN) and microcystins (MC) are cyanotoxins that can occur simultaneously in contaminated water and food. CYN/MC-LR mixtures previously investigated in vitro showed an induction of micronucleus (MN) formation only in the presence of the metabolic fraction S9. When this is the case, the European Food Safety Authority recommends a follow up to in vivo testing. Thus, rats were orally exposed to 7.5 + 75, 23.7 + 237, and 75 + 750 μg CYN/MC-LR/kg body weight (b.w.). The MN test in bone marrow was performed, and the standard and modified comet assays were carried out to measure DNA strand breaks or oxidative DNA damage in stomach, liver, and blood cells. The results revealed an increase in MN formation in bone marrow, at all the assayed doses. However, no DNA strand breaks nor oxidative DNA damage were induced, as shown in the comet assays. The histopathological study indicated alterations only in the highest dose group. Liver was the target organ showing fatty degeneration and necrotic hepatocytes in centrilobular areas, as well as a light mononuclear inflammatory periportal infiltrate. Additionally, the stomach had flaking epithelium and mild necrosis of epithelial cells. Therefore, the combined exposure to cyanotoxins may induce genotoxic and histopathological damage in vivo.
Leticia Díez-Quijada; Concepción Medrano-Padial; María Llana-Ruiz-Cabello; Giorgiana M. Cătunescu; Rosario Moyano; Maria A. Risalde; Ana M. Cameán; Ángeles Jos. Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats. Toxins 2020, 12, 348 .
AMA StyleLeticia Díez-Quijada, Concepción Medrano-Padial, María Llana-Ruiz-Cabello, Giorgiana M. Cătunescu, Rosario Moyano, Maria A. Risalde, Ana M. Cameán, Ángeles Jos. Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats. Toxins. 2020; 12 (6):348.
Chicago/Turabian StyleLeticia Díez-Quijada; Concepción Medrano-Padial; María Llana-Ruiz-Cabello; Giorgiana M. Cătunescu; Rosario Moyano; Maria A. Risalde; Ana M. Cameán; Ángeles Jos. 2020. "Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats." Toxins 12, no. 6: 348.
The reduction of sulfur dioxide in wine is a consumer’s demand, considering the allergic effects that may occur in people who are sensitive to it. Stilbenes are candidates of great interest for this purpose because of their antioxidant/antimicrobial activities and health properties, and also because they are naturally found in the grapevine. In the present study, the in vitro toxicity of an extract from grapevine shoots (with a stilbene richness of 45.4%) was assessed in two human cell lines. Significant damage was observed from 30 μg/mL after 24 h, and 40 µg/mL after 48 h of exposure. Similarly, the ultrastructural study revealed a significant impairment of cell growing. The extract was able to protect cells against an induced oxidative stress at all concentrations studied. In view of the promising results, a more exhaustive toxicological assessment of the extract is needed to confirm the safety of its further use as additive in wine.
Concepción Medrano-Padial; María Puerto; F. Javier Moreno; Tristan Richard; Emma Cantos-Villar; Silvia Pichardo. In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry. Antioxidants 2019, 8, 467 .
AMA StyleConcepción Medrano-Padial, María Puerto, F. Javier Moreno, Tristan Richard, Emma Cantos-Villar, Silvia Pichardo. In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry. Antioxidants. 2019; 8 (10):467.
Chicago/Turabian StyleConcepción Medrano-Padial; María Puerto; F. Javier Moreno; Tristan Richard; Emma Cantos-Villar; Silvia Pichardo. 2019. "In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry." Antioxidants 8, no. 10: 467.