Effect of oral administration of green tea extract in various dosage schemes on oxidative stress status of mice in vivo

Green tea is a favorite beverage and its extracts are popular components of dietary supplements. The aim of the present in vivo study was to obtain detailed information about the effect of a standard green tea extract (Polyphenon, P), at different doses, on antioxidant enzymes and oxidative stress markers in murine blood, liver, small and large intestine. In all doses, P improved the oxidative stress status via an increased content of plasmatic SH-groups (by 21–67 %). Regarding antioxidant enzymes in tissues, the low dose of P had the best effect as it elevated the activity of NADPH/quinone reductase in liver and small intestine, thioredoxin reductase in small intestine and hepatic superoxide dismutase. Based on these facts, consumation of green tea seems to be safe and beneficial, while consumption of dietary supplements containing high doses of catechins may disturb oxidative balance by lowering the activity of thioredoxin reductase, glutathione S-transferase, glutathione reductase and superoxide dismutase

Effect of selected catechins on doxorubicin antiproliferative efficacy and hepatotoxicity in vitro

Catechins may influence both desirable and undesirable effects of many drugs. In this study, the in vitro effect of (+)-catechin, (–)-epicatechin, (–)-epigallocatechin, (–)-epicatechingallate, and (–)-epigallocatechingallate (EGCG)on the efficacy of anticancer drug doxorubicin (DOX) was studiedin HCT-8 cancer cells.Rat hepatocytes were used to study the influence of EGCG on DOX hepatotoxicity. Cell proliferation and viability were studied by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide and neutral red uptake assays. Formation of reactive oxigen species was determined using the dichlorofluorescein assay. All of the studied catechins(1–25 µmol L–1) had no effect on the proliferation of intestinal cancer cells and did not affect the antiproliferative effect of DOX (1–8 µmol L–1) in these cells. Moreover, EGCG at 25 µmol L–1 increased the viability of isolated hepatocytes and significantly protected these cells against DOX-induced toxicity and ROS production. Consumption of EGCG during DOX therapy seems to be safe and beneficial, since EGCG does not decrease DOX anticancer efficacy and could ameliorate DOX hepatotoxicity

Natural compounds with potential antioxidant activity; in vitro study in a model of protein glycoxidation

1. SUMMARY IN CZECH (ABSTRACT) Reaktivní formy kyslíku a dusíku (RONS) a volné radikály se staly v posledním desetiletí významným předmětem studia v mnoha oborech včetně medicínských. Stav, při němž je rovnováha mezi vznikem a odbouráváním volných radikálů v organismu posunuta ve prospěch jejich vzniku, se nazývá oxidační stres. Při nadbytku volných radikálů v organismu dochází k poškození biomolekul a tkání, což může vést až ke vzniku onemocnění. Oxidační stres se podílí na vzniku celé řady onemocnění, např. diabetu mellitu, aterosklerózy, revmatoidní artritidy, Alzheimerovy choroby a dalších, ale také na fyziologickém procesu stárnutí. Ve snaze pozastavit průběh stárnutí a odvrátit vznik onemocnění se začala používat různá potravní aditiva s obsahem vitamínů a antioxidantů přírodního původu. Diabetes mellitus je onemocnění charakterizované hyperglykémií a je vždy provázeno oxidačním stresem. Glukóza a různé intracelulární cukry (fruktóza, ribóza, glyceraldehyd a další) se kovalentně váží na volné aminoskupiny proteinů a způsobují poškození jejich struktury. Tento proces se nazývá neenzymová glykace. Sledem následných reakcí vznikají pozdní produkty pokročilé glykace (AGEs), které se podílí na tvorbě kovalentních vazeb mezi sousedními molekulami proteinů (crosslinks). Mezi nejvýznamnější AGEs patří N--..

Látky přírodního původu s potenciální antioxidační aktivitou; studie in vitro na modelu glykoxidace proteinů.

1. SUMMARY IN CZECH (ABSTRACT) Reaktivní formy kyslíku a dusíku (RONS) a volné radikály se staly v posledním desetiletí významným předmětem studia v mnoha oborech včetně medicínských. Stav, při němž je rovnováha mezi vznikem a odbouráváním volných radikálů v organismu posunuta ve prospěch jejich vzniku, se nazývá oxidační stres. Při nadbytku volných radikálů v organismu dochází k poškození biomolekul a tkání, což může vést až ke vzniku onemocnění. Oxidační stres se podílí na vzniku celé řady onemocnění, např. diabetu mellitu, aterosklerózy, revmatoidní artritidy, Alzheimerovy choroby a dalších, ale také na fyziologickém procesu stárnutí. Ve snaze pozastavit průběh stárnutí a odvrátit vznik onemocnění se začala používat různá potravní aditiva s obsahem vitamínů a antioxidantů přírodního původu. Diabetes mellitus je onemocnění charakterizované hyperglykémií a je vždy provázeno oxidačním stresem. Glukóza a různé intracelulární cukry (fruktóza, ribóza, glyceraldehyd a další) se kovalentně váží na volné aminoskupiny proteinů a způsobují poškození jejich struktury. Tento proces se nazývá neenzymová glykace. Sledem následných reakcí vznikají pozdní produkty pokročilé glykace (AGEs), které se podílí na tvorbě kovalentních vazeb mezi sousedními molekulami proteinů (crosslinks). Mezi nejvýznamnější AGEs patří N--...Katedra biochemických vědDepartment of Biochemical SciencesFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

The Hepatotoxicity of Alantolactone and Germacrone: Their Influence on Cholesterol and Lipid Metabolism in Differentiated HepaRG Cells

The sesquiterpenes alantolactone (ATL) and germacrone (GER) are potential anticancer agents of natural origin. Their toxicity and biological activity have been evaluated using the differentiated HepaRG (dHepaRG) cells, a hepatocyte-like model. The half-maximal inhibitory concentrations of cell viability after 24-h treatment of dHepaRG cells are approximately 60 M for ATL and 250 M for GER. However, both sesquiterpenes induce reactive oxygen species (ROS) formation in non-toxic concentrations and significantly dysregulate the mRNA expression of several functional markers of mature hepatocytes. They similarly decrease the protein level of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) and their transcription target, intercellular adhesion molecule 1 (ICAM-1). Based on the results of a BATMAN-TCM analysis, the effects of sesquiterpenes on cholesterol and lipid metabolism were studied. Sesquiterpene-mediated dysregulation of both cholesterol and lipid metabolism was observed, during which these compounds influenced the protein expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and sterol regulatory element-binding protein 2 (SREBP-2), as well as the mRNA expression of HMGCR, CYP19A1, PLIN2, FASN, SCD, ACACB, and GPAM genes. In conclusion, the two sesquiterpenes caused ROS induction at non-toxic concentrations and alterations in cholesterol and lipid metabolism at slightly toxic and toxic concentrations, suggesting a risk of liver damage if administered to humans

Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes

Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer. In our study, SFN alone did not significantly alter the activity and expression of the studied DMEs, except for the glutathione S-transferase (GSTA1) mRNA level, which was significantly enhanced. Co-treatment of hepatocytes with SFN and BNF led to a substantial increase in sulfotransferase, aldoketoreductase 1C, carbonylreductase 1 and NAD(P)H:quinone oxidoreductase 1 activity and a marked decrease in cytochrome P450 (CYP) Cyp1a1, Cyp2b and Cyp3a4 expression in comparison to the treatment with BNF alone. Sulforaphane is able to modulate the activity and/or expression of DMEs, thus shifting the balance of carcinogen metabolism toward deactivation, which could represent an important mechanism of its chemopreventive activity

Effect of Green Tea Extract-Enriched Diets on Insulin and Leptin Levels, Oxidative Stress Parameters and Antioxidant Enzymes Activities in Obese Mice

Green tea and green tea extracts (GTE) are often incorporated into diet intended to weight reduction, although the information about their efficacy in obese individuals is insufficient. The present study was designed to follow up the effect of defined and standardized GTE in mice with obesity induced by monosodium L-glutamate. Obese mice were fed with GTE-supplemented diet in three dosage regimens: 28-day and 3-day intake of 1 g GTE in 1 kg of diet and 28-day intake of 0.1 g GTE in 1 kg of diet. The information on body weight, food intake, oxidation stress parameters in blood and antioxidant enzymes activity in liver and small intestine was obtained. High doses of GTE decreased the specific activities of glutathione reductase and catalase and increased concentrations of malondialdehyde in blood. Specific activities of antioxidant enzymes in the liver and small intestine were not altered after GTE treatment except the decrease of NAD(P)H:quinone oxidoreductase activity. Our results showed that GTE did not affect average body weight and did not markedly improve antioxidant status in glutamate-induced obese mice. Moreover, intake of high doses of GTE made antioxidant defense in obese animals even worse

Antiproliferative Effects of Hop-derived Prenylflavonoids and Their Influence on the Efficacy of Oxaliplatine, 5-fluorouracil and Irinotecan in Human ColorectalC Cells

Beer, the most popular beverage containing hops, is also frequently consumed by cancer patients. Moreover, non-alcoholic beer, owing to its nutritional value and high content of biological active compounds, is sometimes recommended to patients by oncologists. However, the potential benefits and negatives have to date not been sufficiently evaluated. The present study was designed to examine the effects of four main hop-derived prenylflavonoids on the viability, reactive oxygen species (ROS) formation, activity of caspases, and efficiency of the chemotherapeutics 5-fluorouracil (5-FU), oxaliplatin (OxPt) and irinotecan (IRI) in colorectal cancer cell lines SW480, SW620 and CaCo-2. All the prenylflavonoids exerted substantial antiproliferative effects in all cell lines, with xanthohumol being the most effective (IC50 ranging from 3.6 to 7.3 µM). Isoxanthohumol increased ROS formation and the activity of caspases-3/7, but 6-prenylnaringenin and 8-prenylnaringenin exerted antioxidant properties. As 6-prenylnaringenin acted synergistically with IRI, its potential in combination therapy deserves further study. However, other prenylflavonoids acted antagonistically with all chemotherapeutics at least in one cell line. Therefore, consumption of beer during chemotherapy with 5-FU, OxPt and IRI should be avoided, as the prenylflavonoids in beer could decrease the efficacy of the treatment

Age-Related Changes in Hepatic Activity and Expression of Detoxification Enzymes in Male Rats

Process of aging is accompanied by changes in the biotransformation of xenobiotics and impairment of normal cellular functions by free radicals. Therefore, this study was designed to determine age-related differences in the activities and/or expressions of selected drug-metabolizing and antioxidant enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6-week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using immunoblotting. Remarkable age-related decrease in specific activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes with advancing age were found. On the other hand, specific activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats compared with the young ones, respectively. Interindividual variability in CBR1 activity increased significantly with rising age. We suppose that elevated activities of GST and CBR1 may protect senescent rats against xenobiotic as well as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism of drugs, which are CBR1 and especially GSTs substrates