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1.
Nat Prod Bioprospect ; 13(1): 19, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37284961

RESUMEN

This study investigates the potential of cannabidiol (CBD), one major cannabinoid of the plant Cannabis sativa, alone and in combination with a terpene-enriched extract from Humulus lupulus ("Hops 1"), on the LPS-response of RAW 264.7 macrophages as an established in vitro model of inflammation. With the present study, we could support earlier findings of the anti-inflammatory potential of CBD, which showed a dose-dependent [0-5 µM] reduction in nitric oxide and tumor necrosis factor-alpha (TNF-α) released by LPS-stimulated RAW 264.7 macrophages. Moreover, we observed an additive anti-inflammatory effect after combined CBD [5 µM] and hops extract [40 µg/mL] treatment. The combination of CBD and Hops 1 showed effects in LPS-stimulated RAW 264.7 cells superior to the single substance treatments and akin to the control hydrocortisone. Furthermore, cellular CBD uptake increased dose-dependently in the presence of terpenes from Hops 1 extract. The anti-inflammatory effect of CBD and its cellular uptake positively correlated with terpene concentration, as indicated by comparison with a hemp extract containing both CBD and terpenes. These findings may contribute to the postulations for the so-called "entourage effect" between cannabinoids and terpenes and support the potential of CBD combined with phytomolecules from a non-cannabinoid source, such as hops, for the treatment of inflammatory diseases.

2.
Molecules ; 27(16)2022 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-36014561

RESUMEN

Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.


Asunto(s)
Antioxidantes , COVID-19 , Antioxidantes/metabolismo , Glutatión/metabolismo , Humanos , Peroxidación de Lípido , Estrés Oxidativo , SARS-CoV-2 , Superóxido Dismutasa/metabolismo , Tocoferoles
3.
Molecules ; 27(9)2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35566057

RESUMEN

This work involves a comprehensive chemical composition analysis of leaf and cone samples of Lithuanian hop varieties. This study aimed to determine the chemometric properties of the leaves and cones of five Lithuanian hop varieties. Determined properties were the following: (a) xanthohumol content, (b) phenolic compounds, (c) flavonoids, (d) radical scavenging activity, and (e) the qualitative composition of volatile compounds. The total content of phenolic compounds in aqueous 75% methanolic extracts varied between 31.4-78.2 mg of rutin equivalents (RE)/g, and the concentration of flavonoids was between 11.0-23.3 mg RE/g. Radical scavenging activity varied between 34.4-87.2 mg RE/g. A QUENCHER analysis procedure showed 91.7-168.5 mg RE/g of the total phenolic compound content, 12.7-21.4 mg RE/g of flavonoids, and 48.4-121.0 mg RE/g of radical scavenging activity. 'Fredos taurieji' and 'Fredos derlingieji' varieties have shown maximum values of phenolic compounds and radical scavenging activity both in leaf and cone suspensions. These varieties accumulated a higher amount of xanthohumol in leaves. The concentration of xanthohumol in the samples varied between 0.0014-0.2136% of dry mass, with the highest concentration in the cones of 'Kauno grazieji'. We identified 19 volatile compounds in leaves, and in cones, we identified 32. In both of them, α-humulene and ß caryophyllene dominated. 'Raudoniai' leaves were exceptional in their aroma due to dominating compound nagina ketone (Kovats index 1306). The QUENCHER procedure has shown a great potential for the unextractable residue of hop raw material. Further investigation and valorization of different hop biomass components, not only cones, are essential.


Asunto(s)
Humulus , Flavonoides , Humulus/química , Lituania , Extractos Vegetales/química , Hojas de la Planta/química
4.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34576119

RESUMEN

Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ2 level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ2, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.


Asunto(s)
Apoptosis/efectos de los fármacos , Cannabidiol/farmacología , Queratinocitos/citología , Queratinocitos/efectos de la radiación , Psoriasis/patología , Rayos Ultravioleta , Biomarcadores/metabolismo , Línea Celular , Dinoprostona/farmacología , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Queratinocitos/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación
5.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33540902

RESUMEN

Human epidermal keratinocytes are constantly exposed to UV radiation. As a result, there is a significant need for safe and effective compounds to protect skin cells against this environmental damage. This study aimed to analyze the effect of phytocannabinoid-cannabinoid (CBD)-on the proteome of UVA/B irradiated keratinocytes. The keratinocytes were cultured in a three-dimensional (3D) system, designed to mimic epidermal conditions closely. The obtained results indicate that CBD protected against the harmful effects of UVA/B radiation. CBD decreased the expression of proinflammatory proteins, including TNFα/NFκB and IκBKB complex and decreased the expression of proteins involved in de novo protein biosynthesis, which are increased in UVA/B-irradiated cells. Additionally, CBD enhanced the UV-induced expression of 20S proteasome subunits. CBD also protected protein structures from 4-hydroxynonenal (HNE)-binding induced by UV radiation, which primarily affects antioxidant enzymes. CBD-through its antioxidant/anti-inflammatory activity and regulation of protein biosynthesis and degradation-protects skin cells against UVA/B-induced changes. In the future, its long-term use in epidermal cells should be investigated.


Asunto(s)
Cannabidiol/farmacología , Queratinocitos/efectos de los fármacos , Proteoma/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Rayos Ultravioleta , Aldehídos/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Cannabidiol/química , Técnicas de Cultivo de Célula , Células Cultivadas , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Quinasa I-kappa B/metabolismo , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Estructura Molecular , Complejos Multiproteicos/metabolismo , FN-kappa B/metabolismo , Análisis de Componente Principal , Proteoma/efectos de la radiación , Transducción de Señal/efectos de la radiación , Factor de Necrosis Tumoral alfa/metabolismo
6.
Antioxidants (Basel) ; 10(1)2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33466256

RESUMEN

Satureja hortensis L. is an annual herbaceous plant of the Lamiaceae Lindl. family. S. hortensis L., related to thyme and rosemary, is used as spice and traditional medicinal herb in Europe. Mainly due to the polyphenols contained in S. hortensis L., this plant exhibits multiple biological effects. However, therapeutic effects on cells, including skin tumors, have not yet been studied. Therefore, the aim of this study was to compare the composition and the resulting antioxidant as well as biological properties [on melanocytes and melanoma cells] of summer, savory growing in botanical garden of Vytautas Magnus University in middle Lithuania climatic conditions, collected during various phases of vegetation. It has been shown that the budding phase alcohol extract of this plant contains the largest amounts of polyphenols, including rutin and rosemary acid, which promote the radical scavenging activity and antioxidant properties. In contrast, the extract from the massive flowering phase already at a concentration of 12.5 µg/mL reduces the survival of melanoma cells to 60% with 90% melanocytes survival. In addition, extracts from beginning of flowering and end of flowering at a concentration of 25 µg/mL, containing significantly less rutin and rosmarinic acid, in combination with irradiation of cells with UVB, significantly increased the lipid peroxidation process, particularly in melanoma cells. These data indicate the possibility of using extracts from S. hortensis L. to modulate/differentiate the metabolism of normal and tumor skin cells.

7.
J Pharm Biomed Anal ; 192: 113656, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33086172

RESUMEN

UV phototherapy used in chronic skin diseases causes redox imbalance and pro-inflammatory reactions, especially in the case of unchanged skin cells. To prevent the harmful effects of UV radiation, cannabidiol (CBD) has been used, which has antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to evaluate the effect of CBD on the metabolism of skin keratinocytes in nude rats exposed to UVA/UVB radiation using a proteomic approach. The results obtained with SDS-PAGE/nanoHPLC/QexactiveOrbiTrap show that exposure of rat's skin to UVA/UVB radiation, as well as the action of CBD, significantly modified the expression of proteins involved in inflammation, redox balance and apoptosis. UVA/UVB radiation significantly increased the expression and biological effectiveness of the nuclear factor associated with erythroid factor 2 (Nrf2) and cytoprotective proteins being products of its transcriptional activity, including superoxide dismutase (Cu,Zn-SOD) and the inflammatory response (nuclear receptor coactivator-3 and paralemmin-3), while CBD treatment counteracted and partially eliminated these changes. Moreover, cannabidiol reversed changes in the UV-induced apoptotic pathways by modifying anti-apoptotic and pro-apoptotic factors (apoptosis regulator Bcl-2 and transforming growth factor-ß). The results show that CBD maintains keratinocyte proteostasis and therefore could be suggested as a protective measure in the prevention of UV-induced metabolic changes in epidermal keratinocytes.


Asunto(s)
Cannabidiol , Rayos Ultravioleta , Animales , Cannabidiol/farmacología , Queratinocitos , Proteómica , Ratas , Piel , Rayos Ultravioleta/efectos adversos
8.
Int J Mol Sci ; 21(18)2020 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-32916896

RESUMEN

UVB phototherapy is treatment for psoriasis, which increases phospholipid oxidative modifications in the cell membrane of the skin. Therefore, we carried out lipidomic analysis on the keratinocytes of healthy individuals and patients with psoriasis irradiated with UVB and treated with cannabidiol (CBD), phytocannabinoid with antioxidant and anti-inflammatory properties. Our results showed that, in psoriatic keratinocytes phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), and ether-linked phosphoethanolamine (PEo), were downregulated, while SM (d41:2) was upregulated. These changes were accompanied by an increase in negative zeta potential, which indicates translocation of PS to the outer layer of the membrane. CBD treatment of psoriatic keratinocytes led to downregulation of PC, PS, and upregulation of certain PEo and an SM species, SM (d42:2), and the zeta potential. However, UVB irradiation of psoriatic keratinocytes resulted in upregulation of PC, PC plasmalogens (PCp), PEo, and a decrease in the negative zeta potential. The exposure of UVB-irradiated cells to CBD led to a decrease in the level of SM (d42:2). Our results suggest that CBD induces pro-apoptotic mechanisms in psoriatic keratinocytes while simultaneously improving the antioxidant properties and preventing the loss of transepidermal water of keratinocytes of patients irradiated with UVB. Thus, CBD has potential therapeutic value in the treatment of psoriasis.


Asunto(s)
Cannabidiol/uso terapéutico , Queratinocitos/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Fosfolípidos/metabolismo , Psoriasis/tratamiento farmacológico , Adulto , Cannabidiol/farmacología , Estudios de Casos y Controles , Femenino , Humanos , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Metabolismo de los Lípidos/efectos de la radiación , Masculino , Persona de Mediana Edad , Cultivo Primario de Células , Psoriasis/metabolismo , Psoriasis/radioterapia , Rayos Ultravioleta , Terapia Ultravioleta , Adulto Joven
9.
Free Radic Biol Med ; 157: 128-153, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31756524

RESUMEN

Modern analytical methods combined with the modern concepts of redox signaling revealed 4-hydroxy-2-nonenal (4-HNE) as particular growth regulating factor involved in redox signaling under physiological and pathophysiological circumstances. In this review current knowledge of the relevance of 4-HNE as "the second messenger of reactive oxygen species" (ROS) in redox signaling of representative major stress-associated diseases is briefly summarized. The findings presented allow for 4-HNE to be considered not only as second messenger of ROS, but also as one of fundamental factors of the stress- and age-associated diseases. While standard, even modern concepts of molecular medicine and respective therapies in majority of these diseases target mostly the disease-specific symptoms. 4-HNE, especially its protein adducts, might appear to be the bioactive markers that would allow better monitoring of specific pathophysiological processes reflecting their complexity. Eventually that could help development of advanced integrative medicine approach for patients and the diseases they suffer from on the personalized basis implementing biomedical remedies that would optimize beneficial effects of ROS and 4-HNE to prevent the onset and progression of the illness, perhaps even providing the real cure.


Asunto(s)
Aldehídos , Estrés Oxidativo , Humanos , Peroxidación de Lípido , Oxidación-Reducción
10.
Arch Dermatol Res ; 311(3): 203-219, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30783768

RESUMEN

The combination of ascorbic acid and rutin is frequently used in oral preparations. However, despite numerous protective effects of each component individually, their combined effect on ultraviolet (UV)-irradiated skin cells has never been evaluated. The aim of this study was to evaluate the combined effect of ascorbic acid and rutin on human keratinocytes and fibroblasts exposed to UVA and UVB radiation. Skin keratinocytes and fibroblasts exposed to UVA and UVB radiation were treated with ascorbic acid or/and rutin. The total antioxidant properties of both components, as well as their effect on cellular pro- and antioxidant status, lipid and protein oxidation, transmembrane transport, and pro-inflammatory and pro/antiapoptotic protein expression were measured. The combination of ascorbic acid and rutin had higher antioxidant properties compared to the activity of the single compound alone, and showed a stronger effect against UV-induced reactive oxygen species generation. The ascorbic acid and rutin combination also showed increased antioxidant enzyme activity (catalase, superoxide dismutase, thioredoxin reductase), which was impaired following UV irradiation. Moreover, ascorbic acid additional stimulated UV-induced bilitranslocase activity responsible for rutin transport, and therefore favored rutin effect on Nrf2 pathway, simultaneously differentiating the reaction of keratinocytes and fibroblasts. In keratinocytes, Nrf2 is strongly activated, while in fibroblasts decreased Nrf2 activity was observed. Used mixture, also significantly silenced UV-induced expression of pro-inflammatory factor NFκB and pro-apoptotic proteins such as caspases 3, 8, and 9. These results showed that ascorbic acid and rutin are complementary in their antioxidant actions, transport and signaling functions. Their combined antioxidant, antiinflammatory and antiapoptotic actions suggest rutin and ascorbic acid are a potentially cytoprotective team against UV-induced skin damage.


Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Ácido Ascórbico/farmacología , Fibroblastos/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Rutina/farmacología , Piel/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Antiinflamatorios/farmacología , Apoptosis/efectos de la radiación , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Ceruloplasmina/metabolismo , Quimioterapia Combinada , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/efectos de la radiación , Humanos , Queratinocitos/metabolismo , Queratinocitos/patología , Queratinocitos/efectos de la radiación , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de la radiación , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación
11.
Antioxidants (Basel) ; 7(8)2018 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-30110920

RESUMEN

Evening primrose (Oenothera L.) is a plant belonging to the family Onagraceae, in which the most numerous species is Oenothera biennis. Some plants belonging to the genus Oenothera L. are characterized by biological activity. Therefore, studies were conducted to determine the dependence of biological activity on the chemical composition of various parts of the evening primrose, mainly leaves, stems, and seeds. Common components of all parts of the Oenothera biennis plants are fatty acids, phenolic acids, and flavonoids. In contrast, primrose seeds also contain proteins, carbohydrates, minerals, and vitamins. Therefore, it is believed that the most interesting sources of biologically active compounds are the seeds and, above all, evening primrose seed oil. This oil contains mainly aliphatic alcohols, fatty acids, sterols, and polyphenols. Evening primrose oil (EPO) is extremely high in linoleic acid (LA) (70⁻74%) and γ-linolenic acid (GLA) (8⁻10%), which may contribute to the proper functioning of human tissues because they are precursors of anti-inflammatory eicosanoids. EPO supplementation results in an increase in plasma levels of γ-linolenic acid and its metabolite dihomo-γ-linolenic acid (DGLA). This compound is oxidized by lipoxygenase (15-LOX) to 15-hydroxyeicosatrienoic acid (15-HETrE) or, under the influence of cyclooxygenase (COX), DGLA is metabolized to series 1 prostaglandins. These compounds have anti-inflammatory and anti-proliferative properties. Furthermore, 15-HETrE blocks the conversion of arachidonic acid (AA) to leukotriene A4 (LTA4) by direct inhibition of 5-LOX. In addition, γ-linolenic acid suppresses inflammation mediators such as interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and cytokine - tumor necrosis factor α (TNF-α). The beneficial effects of EPO have been demonstrated in the case of atopic dermatitis, psoriasis, Sjögren's syndrome, asthma, and anti-cancer therapy.

12.
Metab Brain Dis ; 30(1): 183-90, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25108595

RESUMEN

The aims of this study were to investigate the influences of sweet grass on chronic ethanol-induced oxidative stress in the rat brain. Chronic ethanol intoxication decreased activities and antioxidant levels resulting in enhanced lipid peroxidation. Administration of sweet grass solution to ethanol-intoxicated rats partially normalized the activity activities of Cu,Zn-superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as levels of reduced glutathione and vitamins C, E, and A. Sweet grass also protected unsaturated fatty acids (arachidonic and docosahexaenoic) from oxidations and decreased levels of lipid peroxidation products: 4-hydroxynonenal, isoprostanes, and neuroprostanes. The present in vivo study confirms previous in vitro data demonstrating the bioactivity of sweet grass and suggests a possible role for sweet grass in human health protection from deleterious consequences associated with oxidative stress formation.


Asunto(s)
Intoxicación Alcohólica/tratamiento farmacológico , Antioxidantes/uso terapéutico , Encéfalo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Poaceae/química , Intoxicación Alcohólica/metabolismo , Animales , Catalasa/análisis , Cumarinas/análisis , Evaluación Preclínica de Medicamentos , Etanol/toxicidad , Glutatión/análisis , Glutatión Peroxidasa/análisis , Glutatión Reductasa/análisis , Peroxidación de Lípido/efectos de los fármacos , Masculino , Extractos Vegetales/química , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Vitaminas
13.
Environ Toxicol Pharmacol ; 35(2): 247-53, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23353548

RESUMEN

Changes in the composition and physicochemical properties of liver cell membranes due to ethanol intoxication are due mainly to reactive oxygen species (ROS). The destructive action of free radicals can be neutralized by administration of antioxidants. The purpose of this study was to investigate the efficacy of sweet grass on the physicochemical and biochemical properties of the rat liver membrane altered by chronic ethanol intoxication. Qualitative and quantitative composition of phospholipids and proteins in the membrane were determined by HPLC. Ethanol increased phospholipid levels and altered the level of integral proteins as determined by decreased phenylalanine, cysteine and lysine. Ethanol significantly enhanced changes in the surface charge density of the liver cell membranes as determined by electrophoresis. Administration of sweet grass to rats intoxicated with ethanol significantly protects lipids and proteins against oxidative modifications. Therefore, sweet grass protects against some of the deleterious membrane changes associated with ethanol exposure.


Asunto(s)
Intoxicación Alcohólica/metabolismo , Membrana Celular/efectos de los fármacos , Hígado/efectos de los fármacos , Fosfolípidos/metabolismo , Extractos Vegetales/farmacología , Poaceae/química , Sustancias Protectoras/farmacología , Animales , Membrana Celular/química , Cromatografía Líquida de Alta Presión , Etanol/toxicidad , Hígado/citología , Masculino , Fosfolípidos/análisis , Ratas , Ratas Wistar
14.
Exp Toxicol Pathol ; 65(1-2): 173-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21920720

RESUMEN

Ethanol intoxication is accompanied by oxidative stress formation. Consequently, it leads to disturbances in cellular metabolism that can alter the structure and function of cell membrane components. Black tea displays antioxidant properties, protects membrane phospholipids and may protect integral membrane proteins. In the present study, we examined whether black tea induces changes in the liver integral membrane proteins of 12-months old rats chronically intoxicated with ethanol. To estimate qualitatively and quantitatively the levels of the liver integral membrane proteins, the proteins were selectively hydrolyzed by trypsin, the obtained peptides were resolved by HPLC and the levels of specific amino acids within the individual peptides were determined. All of the obtained peptides contained phenylalanine (Phe), cysteine (Cys) and lysine (Lys). Compared to the control group, rats in the ethanol intoxication group showed decreased liver levels of integral membrane proteins as well as fewer trypsin-hydrolyzed peptides and amino acids in the hydrolyzed peptides. Administration of black tea to ethanol-intoxicated rats partially protected proteins against the structural changes caused by ethanol. Black tea prevented decreases in the levels of cysteine (in about 90% of cases), lysine (in about 60% of cases), phenylalanine (in about 70% of cases) and examined peptides (in about 60% of cases). The liver protein level was higher (by about 18%) in rats who received black tea and ethanol than in those who received ethanol alone. In conclusion, black tea partially protects the composition and level of rat liver cell integral membrane proteins against changes caused by ethanol intoxication.


Asunto(s)
Antioxidantes/farmacología , Camellia sinensis/química , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Aminoácidos/análisis , Animales , Antioxidantes/aislamiento & purificación , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Cromatografía Líquida de Alta Presión , Etanol/toxicidad , Hidrólisis , Hígado/metabolismo , Masculino , Proteínas de la Membrana/análisis , Ratas , Ratas Wistar ,
15.
Free Radic Res ; 44(10): 1216-62, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20836663

RESUMEN

Abstract The current understanding of the complex role of ROS in the organism and pathological sequelae of oxidative stress points to the necessity of comprehensive studies of antioxidant reactivities and interactions with cellular constituents. Studies of antioxidants performed within the COST B-35 action has concerned the search for new natural antioxidants, synthesis of new antioxidant compounds and evaluation and elucidation of mechanisms of action of both natural and synthetic antioxidants. Representative studies presented in the review concern antioxidant properties of various kinds of tea, the search for new antioxidants of herbal origin, modification of tocopherols and their use in combination with selenium and properties of two promising groups of synthetic antioxidants: derivatives of stobadine and derivatives of 1,4-dihydropyridine.


Asunto(s)
Antioxidantes/síntesis química , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Carbolinas/química , Carbolinas/farmacología , Dihidropiridinas/química , Dihidropiridinas/farmacología , Humanos , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología , Compuestos de Selenio/química , Compuestos de Selenio/farmacología , Té/química , Tocoferoles/química , Tocoferoles/farmacología
16.
J Stud Alcohol ; 67(4): 510-8, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16736070

RESUMEN

OBJECTIVE: Black tea has been recently ascertained as a source of water-soluble antioxidants that may enhance cellular antioxidant abilities. The present study was designed to investigate the efficacy of the preventive effect of black tea on oxidative modifications of liver lipids and proteins of 2-month-old rats intoxicated chronically (28 days) with ethanol. METHOD: Lipid peroxidation was estimated by measurement of lipid hydroperoxides, malondialdehyde, and 4-hydroxynonenal by high-performance liquid chromatography (HPLC) and by spectrophotometric determination of conjugated dienes. The markers of protein oxidative modification products-bistyrosine and tryptophan-were quantified by spectrofluorimetry, whereas levels of amino, sulfhydryl, and carbonyl groups were estimated spectrophotometrically. RESULTS: Ethanol intoxication caused changes in liver antioxidant abilities that led to the generation of oxidative stress and, consequently, to the significant increase in products of lipid and protein oxidative modification. Enhanced lipid peroxidation was confirmed by assessment of the concentration of lipid peroxidation products measured at all examined levels. Protein modifications were evidenced by increase in levels of bistyrosine and carbonyl groups and by decrease in concentration of tryptophan and levels of sulfhydryl and amino groups. The metabolic consequences of oxidative modifications of lipids and proteins were reduced by cathepsin B activity and translocation of this lysosomal protease into cytosol as well as markers of liver damage-alanine aminotransferase (ALT) and aspartate aminotransferase (AST)-into the blood serum. Administration of black tea to ethanol-intoxicated rats partially protected antioxidant parameters and, remarkably, prevented the significant increase in concentrations of all measured lipid peroxidation products. Moreover, the levels of markers of the protein-modification process were similar to those of the control group. Protection of biological membranes by black tea prevents changes in the permeability of these membranes and translocation of the examined enzymes. CONCLUSIONS: Our findings indicate that black tea protects proteins and lipids against oxidative modification induced by chronic ethanol intoxication, which preserves changes in redox and proteolytic homeostasis.


Asunto(s)
Alcoholismo/metabolismo , Antioxidantes/farmacología , Camellia sinensis , Etanol/farmacología , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Alcoholismo/sangre , Animales , Aspartato Aminotransferasas/sangre , Catepsina B/metabolismo , Etanol/efectos adversos , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar
17.
Bioelectrochemistry ; 69(2): 142-7, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16545623

RESUMEN

The cell membrane is an extremely complicated object. It participates in a large number of equilibria. For this reason, it is impossible to determine the parameters of all of them. It is the purpose of this work to define a limited number of averaged parameters in order to describe the equilibria between cell membrane components and environmental components. These parameters are the total acidic functional group concentration as well as the basic group concentration and their association constants with hydrogen or hydroxyl ions. The parameters were determined using the pH dependence of the electric surface charge density. The usefulness of these parameters was checked by studying the effect of green tea on liver cells in ethanol poisoning. Ethanol provokes an increase in concentration of functional groups, positively and negatively charged, as well as an increase in the basic groups association constant and a decrease in acidic groups association constant. Administering green tea partly compensates the changes provoked by ethanol poisoning. The parameters proposed in this work, C(TA), C(TB), K(AH) and K(BOH), are suited for monitoring the changes caused by various factors.


Asunto(s)
Equilibrio Ácido-Base/fisiología , Membrana Celular/química , Membrana Celular/fisiología , Hepatocitos/fisiología , Modelos Biológicos , Extractos Vegetales/administración & dosificación , Equilibrio Ácido-Base/efectos de los fármacos , Animales , Células Cultivadas , Simulación por Computador , Etanol/administración & dosificación , Hepatocitos/efectos de los fármacos , Concentración de Iones de Hidrógeno , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratas , Ratas Wistar , Té/metabolismo
18.
Nutrition ; 21(9): 925-32, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16084066

RESUMEN

OBJECTIVE: The present study investigated the influence of green tea as a source of water-soluble antioxidants on the liver antioxidant potential of different aged rats chronically intoxicated with ethanol. METHODS: Rats (2, 12, and 24 mo old) were fed for 5 wk on a control or an ethanol Lieber-DeCarli diet with and without green tea (7 g/L). The activity and level of enzymatic and non-enzymatic antioxidants and the level of markers of protein and lipid oxidation in the liver of rats were examined. RESULTS: The activities of superoxide dismutase and catalase and levels of vitamins C, E, A, and beta-carotene were significantly decreased, whereas activities of glutathione peroxidase and glutathione reductase and the level of reduced glutathione significantly increased during aging. The ethanol diet caused a significant decrease in activity of antioxidant enzymes and in the level of non-enzymatic antioxidants tested. Administration of green tea to ethanol-treated rats of different ages partly normalized the activity of enzymes and the level of non-enzymatic antioxidants. Changes in antioxidant ability observed during aging were accompanied by increased levels of markers of lipid and protein modifications that also were intensified by ethanol. Green tea caused a decrease in lipid and protein oxidation in aged and ethanol-treated rats. The protective effect of green tea was confirmed by the significantly lower activity of biomarkers of liver damage (alanine and aspartate aminotransferases) in the serum of rats that received green tea with ethanol compared with rats from the control ethanol group. CONCLUSIONS: The use of green tea appears to be beneficial to rat liver by decreasing oxidative stress caused by ethanol and/or aging.


Asunto(s)
Envejecimiento/metabolismo , Antioxidantes/administración & dosificación , Etanol/toxicidad , Hígado/metabolismo , Estrés Oxidativo/efectos de los fármacos , , Factores de Edad , Envejecimiento/sangre , Animales , Catalasa/sangre , Catalasa/metabolismo , Glutatión/sangre , Glutatión/metabolismo , Glutatión Peroxidasa/sangre , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/sangre , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Estrés Oxidativo/fisiología , Distribución Aleatoria , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismo , Té/química , Vitaminas/sangre
19.
Chem Biol Interact ; 156(1): 41-53, 2005 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-16098958

RESUMEN

It is known that aging is characterized by changes in cell metabolism resulting in modification of the structure and function of cell membrane components which is mainly the consequence of reactive oxygen species action. These disturbances are also enhanced by different xenobiotics, e.g. ethanol. Therefore, the aim of this paper is to examine green tea influence on total antioxidant status (TAS) and on composition and electric charge of erythrocyte membrane phospholipids in ethanol intoxicated rats of various ages. Antioxidant abilities of erythrocytes were estimated by measuring TAS. Qualitative and quantitative composition of phospholipids in the membrane was determined by HPLC, while the extent of erythrocytes lipid peroxidation was estimated by HPLC measurement of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels. Electrophoresis was used to determine the surface charge density of the rat erythrocyte membrane. It was shown that the process of aging was accompanied by a decrease in TAS and in the total amount of phospholipids as well as by enhancement of lipid peroxidation and increase in surface charge density of erythrocyte membrane. Ethanol administration caused, in term, decrease in TAS and increase in the level of all phospholipids and lipid peroxidation products. Ethanol as well significantly enhanced changes in surface charge density of erythrocyte membrane. The ingestion of green tea partially prevented decrease in erythrocyte antioxidant abilities observed during aging and ethanol intoxication. Moreover, long-term drinking of green tea protects the structure of the erythrocytes membrane disturbed during aging process and/or chronic ethanol intoxication.


Asunto(s)
Membrana Eritrocítica/efectos de los fármacos , Etanol/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Fosfolípidos/metabolismo , Té/química , Envejecimiento , Aldehídos/análisis , Aldehídos/metabolismo , Animales , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Electroforesis , Membrana Eritrocítica/metabolismo , Malondialdehído/análisis , Malondialdehído/metabolismo , Fosfolípidos/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas
20.
Artículo en Polaco | MEDLINE | ID: mdl-15928598

RESUMEN

Coenzyme Q10 (ubiquinone) is a naturally occurring compound widely distributed in animal organisms and in humans. The primary compounds involved in the biosynthesis of ubiquinone are 4-hydroxybenzoate and the polyprenyl chain. An essential role of coenzyme Q10 is as an electron carrier in the mitochondrial respiratory chain. Moreover, coenzyme Q10 is one of the most important lipophilic antioxidants, preventing the generation of free radicals as well as oxidative modifications of proteins, lipids, and DNA, it and can also regenerate the other powerful lipophilic antioxidant, alpha-tocopherol. Antioxidant action is a property of the reduced form of coenzyme Q10, ubiquinol (CoQ10H2), and the ubisemiquinone radical (CoQ10H*). Paradoxically, independently of the known antioxidant properties of coenzyme Q10, the ubisemiquinone radical anion (CoQ10-) possesses prooxidative properties. Decreased levels of coenzyme Q10 in humans are observed in many pathologies (e.g. cardiac disorders, neurodegenerative diseases, AIDS, cancer) associated with intensive generation of free radicals and their action on cells and tissues. In these cases, treatment involves pharmaceutical supplementation or increased consumption of coenzyme Q10 with meals as well as treatment with suitable chemical compounds (i.e. folic acid or B-group vitamins) which significantly increase ubiquinone biosynthesis in the organism. Estimation of coenzyme Q10 deficiency and efficiency of its supplementation requires a determination of ubiquinone levels in the organism. Therefore, highly selective and sensitive methods must be applied, such as HPLC with UV or coulometric detection.


Asunto(s)
Antioxidantes/metabolismo , Antioxidantes/farmacología , Ubiquinona/análogos & derivados , Animales , Coenzimas , Citoprotección , Radicales Libres/metabolismo , Humanos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Ubiquinona/biosíntesis , Ubiquinona/metabolismo , Ubiquinona/farmacología
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