Oral Administration Of Green Tea Research Articles

Green Tea Alters Bile Acid Micellar Solubility of Raloxifene

Green tea is a popular botanical natural product, and its consumption has been associated with pharmacokinetic natural product‐drug interactions (NP‐DIs). Unpublished clinical data show that acute and chronic oral administration of green tea decreased the systemic exposure of raloxifene in healthy subjects. These clinical data indicate an intestinal interaction, although the mechanism for reduced absorption and systemic exposure is not known. NP‐mediated modulation of drug solubility in the intestinal lumen is an area of increasing interest and concern. Intestinal bile acids can enhance the absorption of hydrophobic compounds by micellar solubilization, and raloxifene is a Biopharmaceutic Drug Disposition Classification System (BDDCS) class 2 drug with poor water solubility. We hypothesize that green tea reduces intestinal absorption of raloxifene through decreased micellar solubility. To investigate this interaction, bile acid mixed micelles were prepared and incubated with raloxifene, green tea extract (GTE), (‐)‐epigallocatechin gallate EGCG, and a combination of raloxifene with GTE or EGCG. The size of the micelles was determined by dynamic light scattering and raloxifene quantification was determined by UPLC‐MS/MS. Raloxifene did not affect micelle diameter (micelle alone: 63.2 ± 5.6 nm, micelle with raloxifene 76.0 ± 5.8). In contrast, micelle diameter increased after incubation with GTE (416 ± 150.3 nm), EGCG (300.9 ± 173 nm), raloxifene + GTE (451 ± 164.2 nm), and raloxifene + EGCG (294.8 ± 303 nm). The micellar solubility of raloxifene was decreased by ~80% after incubation with GTE, whereas EGCG produced inconsistent results. These data suggest GTE decreased the micellar solubility of raloxifene and may play a role in the observed green tea‐raloxifene intestinal interaction.

The effect of oral administration of green tea and ginger extracts on blood glucose in diabetic rats.

In recent years,green tea and ginger have become a subject of interest because of their beneficial effects on human health. The aim of the present study was to compare the effect of long term administration of green tea and ginger each alone to the effect of their combination on blood glucose level in streptozotocin-induced diabetic rats. Method: A group of 50 male albino rats was divided into five groups (10 rats each group). The normal control group( NC) administered tap water, other animals were injected by streptozotocin 45mg/Kg body weight intraperitonially to induce diabetes mellitus and then divided into four groups ,diabetic control (DC) without treatment, diabetic group administered green tea extract for four weeks (DGT), diabetic group administered ginger extract for four weeks(DGI), and diabetic group administered mixture of green tea and ginger for four weeks (DGG), then we compare the blood glucose level at 1st,2nd,3rd, and 4th week of experiment. Results:We observed that in groups whose water drink was substituted by green tea and ginger extract, the blood glucose level was significantly( p less than 0.05) reduced as compared to diabetic animals. Importantly, we observed that blood glucose level was near control level when green tea was administered simultaneously with ginger extract.Conclusion: Combination of green tea and ginger may be of great value as hypoglycemic agent in diabetic patients, the synergism of their effect on glucose regulation process is underlying this results.

Oral administration of green tea Epigallocatechin-3-gallate reduces oxidative stress and enhances restoration of cardiac function in diabetic rats receiving autologous transplantation of adipose-derived stem cells

Background Cardio-dysfunction is one of the complications in patients with diabetes mellitus (DM). This paper aimed to investigate if oral administration of green tea Epigallocatechin-3-gallate (EGCG, E) and transplantation of adipose-derived stem cells (ADSC) show cross effects on the treatment of cardiomyopathy in rats with type 1 DM. Materials and methods Wistar male rats were divided into four groups (each group contained 8 animals) including sham, DM (diabetic group), DM + ADSC (DM group with ADSC treatment) and DM + ADSC + E (DM + ADSC group with oral administration of EGCG). Results Pathological parameters including hypertrophy, inflammation, and fibrosis were activated in DM group. By contrast, all parameters were significantly improved in treatment group (DM + ADSC group). In addition, improvement of pathological parameters in DM + ADSC + E was significantly better than DM + ADSC. Conclusion We found that EGCG can increase expression of survival marker in ADSC under high glucose environment and reduce serum oxidative stress in DM rats.

Role of Green Tea in Reducing Epidermal Thickness upon Ultraviolet Light-B Injury in BALB/c Mice

The main environmental source for skin damage is ultraviolet (UV) radiation. Many adverse effects have been recognized as the result of prolonged cutaneous exposure to solar ultraviolet radiation, such as erythema, edema, apoptosis, hyperplastic responses, photo-aging, and skin cancer development. Green tea provides photo-protection against UV radiation through many mechanisms including anti-inflammatory, immunomodulatory, and antioxidant properties. The aim of this study was to evaluate the effect of green tea in reducing epidermal thickness on mouse’s skin exposed to UVB irradiation. Thirty mice (Mus musculusspecies, BALB/c strain) underwent this study and were divided into 3 groups: control group (n=10mice), without UVB exposure and green tea administration; exposure group (n=10mice), which were exposed to UVB light only; and treatment group (n=10mice), which were exposed to UVB light and treated with 1 mL of green tea through oral gavage. Mice from both groups (exposure and treatment) were subjected to UVB irradiation 4 days/week (20 minutes/day, 4 weeks). It concluded that oral administration of green tea was provided photo-protection against UVB induced hyperplasia; therefore, it can be regarded as a natural alternative for photo-protection.

Simultaneous detection of green tea catechins and gallic acid in human serum after ingestion of green tea tablets using ion-pair high-performance liquid chromatography with electrochemical detection

We developed an analytical method for the simultaneous determination of tea catechins and gallic acid (GA) in human serum using ion-pair high-performance liquid chromatography (HPLC) with electrochemical detection. GA was measured to estimate the amount of gallate moiety produced by degradation of gallated catechins ((-)-epicatechin-3-gallate, ECG; (-)-epigallocatechin-3-gallate, EGCG). Ethyl gallate was adopted as an internal standard to correct for the extraction efficiency. To maximize extraction efficiency, a hydrophobic polytetrafluoroethylene (PTFE) filter was selected for pre-treatment prior to separation. HPLC separation was performed using a C18 reversed-phase column with a gradient mobile phase of phosphate buffer (pH 2.5) containing tetrahexylammonium hydrogensulfate as an ion-pair reagent. Using this method, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), ECG, EGCG, ethyl gallate, and GA were detected as single peaks. The resolution values for target analytes were 4.0-13.0 and the mean values of the absolute recoveries of catechins and GA were 77.3-93.9%. The detection limits for catechins and GA in serum were 0.4-3.1ng/mL. The serum catechin levels of eight healthy volunteers after ingestion of a single dose of green tea tablets were measured using this method. The concentration of total catechins (free+conjugated forms) in serum peaked 60min after ingestion. From these results, this method is thought to enable the simultaneous quantification of GA, the hydrolysis product of gallated catechins, and target catechins, and to be sufficiently sensitive for pharmacokinetic studies of catechins following oral administration of green tea.

Effect of green tea on reward learning in healthy individuals: a randomized, double-blind, placebo-controlled pilot study

BackgroundBoth clinical and preclinical studies revealed that regular intake of green tea reduced the prevalence of depressive symptoms, as well as produced antidepressant-like effects in rodents. Evidence proposed that disturbed reward learning has been associated with the development of anhedonia, a core symptom of depression. However, the relationship between green tea and reward learning is poorly investigated. Our goal was to test whether chronic treatment with green tea in healthy subjects affects the process of reward learning and subsequently regulates the depressive symptoms.MethodsSeventy-four healthy subjects participated in a double-blind, randomized placebo-controlled study with oral administration of green tea or placebo for 5weeks. We used the monetary incentive delay task to evaluate the reward learning by measurement of the response to reward trial or no-reward trial. We compared the reaction time of reward responsiveness between green tea and placebo treatment. Furthermore, we selected Montgomery-Asberg depression rating scale (MADRS) and 17-item Hamilton Rating Scale for Depression (HRSD-17) to estimate the depressive symptoms in these two groups.ResultsThe results showed chronic treatment of green tea increased reward learning compared with placebo by decreasing the reaction time in monetary incentive delay task. Moreover, participants treated with green tea showed reduced scores measured in MADRS and HRSD-17 compared with participants treated with placebo.ConclusionsOur findings reveal that chronic green tea increased the reward learning and prevented the depressive symptoms. These results also raised the possibility that supplementary administration of green tea might reverse the development of depression through normalization of the reward function.

Protective effect of green tea on CCl4 induced hepatoxicity in experimental rats

Liver diseases are among the major health problems worldwide. Despite their increasing frequency, high morbidity and mortality, medical management is supposed to be insufficient; no therapy has successfully prevented the progression of hepatic diseases. Green tea is one of the commonly used beverages and considered as powerful antioxidant. This study was designed to investigate the protective effects of green tea administration on CCl4 induced liver cirrhosis in experimental rats. A total of 24 male Wistar rats were selected and divided into 4 experimental groups (6 each) as: Group-1: normal healthy untreated rats; Group-2: CCl4 (0.8 mg/kg) induced cirrhotic rats; Group-3: treated with 5% green tea orally; Group-4: treated with CCl4 (0.8 mg/kg) intraperitoneally once a week for 8 weeks+5% oral administration of green tea. The preventive effects of green tea were measured by means of plasma alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, tissue malondialdehyde (MDA), tissue superoxide dismutase (SOD) and tissue catalase. Induction of cirrhosis by CCl4 was indicated by high levels of plasma ALT, direct bilirubin, tissue MDA and low levels of tissue SOD. Results showed that administration of green tea reduced these changes significantly in cirrhotic rats by putting beneficial effects on antioxidant and liver enzymes as well as total and direct bilirubin. This study convinced the possible protective effect of green tea in relation to antioxidant and liver enzymes. It is also conclusive that the chronic and sub chronic administration of green tea extracts has counter effects on hepatotoxicity caused by CCl4 administration. Key words: Green tea, total and direct bilirubin, cirrhosis, alanine aminotransferase (ALT), alkaline phosphatase (ALP).

Green tea and its role on chemoprevention in vivo of genotoxic damage induced by carcinogenic metals (chromium [VI

Consumption of green tea, by its antioxidant properties, has been associated with beneficial health effects, because antioxidant may play a role in the risk and pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. On the other hand, it has been reported that metal compounds such as chromium [VI] are carcinogenic and can induce genotoxic damage through the Oxidative Stress. Therefore, it is possible that green tea has a protective effect against the genotoxic damage induced by this compounds. To evaluate the effect of oral administration of green tea over the genotoxic damage induced by Cr [VI] by quantification of micronucleus (MN) in polychromatic erythrocytes (EPC). We use mice of CD-1 strain that were randomly divided into the following groups: (i) control, (ii) treatment with green tea, (iii) treatment with chromium trioxide, (iv) treatment with green tea and chromium trioxide. The green tea was administrated via intragastric tube every 12 hours over two days (4 doses of 0.25 ml infusions 1.6 g/7.5 ml) and ad libitum (5.6 ml/day for 10 days infusions of 3.2 g/100 ml), while chromium trioxide was administrated via intraperitoneal (20 mg/kg). Blood samples were obtained from the caudal vein, the number of MN in EPC was assessed at 0, 24, 48 and 72 hours after the treatments. The group treated with green tea showed no significant statistical changes in the average of MN. On the other hand, the group that was dosed with the chromium trioxide showed an increase between 4 and 8 MN, which was statistically significant when compared with control group, which confirmed the genotoxic damage. When the green tea treatment was administered before the application of chromium trioxide, there was a decrease in MN frequencies of 31 and 62% at 72 hours, 20 and 35% at 48 hours and 18 and 31% at 24 hours with intragastric and ad libitum respectively, compared with the group treated only with chromium trioxide. Hence, green tea reduced the genotoxic damage induced by chromium trioxide, and the highest protection was presented at 72 hours. Our findings support the protective effects of green tea against the damage of genetic material, induced by metal compounds such as chromium [VI], suggesting that its antioxidant compounds are those that have a chemopreventive effect on the EOX generated by the Cr [VI] during its reduction to Cr (III). The fact that the largest decrease in the frequency of MN was observed at 72 hours and ad libitum treatment, suggests that, the protective effect depends on the bioavailability, pharmacodynamics and pharmacokinetics of the active ingredient in green tea, so the administration of green tea for a long period of time before the exposure to Cr [VI] could have a more consistent preventive effect.

Identification and dynamic analysis of the purine alkaloids in rat plasma after oral administration of green tea by liquid chromatography hybrid ion trap time-of-flight mass spectrometry

A liquid chromatography hybrid ion trap time-of-flight mass spectrometric (LC–IT-TOF-MS) method was developed and validated for identification and simultaneous determination of the potential bioactive components from green tea in rat plasma. The plasma samples were extracted by liquid–liquid extraction with ethyl acetate and separated on Shim-pack XR-ODS II column by a gradient elution within a runtime of 8.0min. The mobile phase consisted of A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in water) at a flow rate of 0.4ml/min. Two prototype components and one metabolite were successfully identified as caffeine, theobromine and theophylline according to their retention times, accurate molecule weight, and major fragment ions. Then they were determined with the addition of two internal standards, hypoxanthine and paracetamol. The linear range was 10–10,000ng/ml for caffeine, 2.0–2000ng/ml for theobromine and 1.0–1000ng/ml for theophylline, respectively. Intra-day and inter-day precision were within 6.0% and 10.9%, and accuracy was less than 4.8% and 6.5%, respectively. The validated method was successfully applied to investigate the dynamic change rules of caffeine, theobromine and theophylline in rat plasma after oral administration of caffeine, theobromine and green tea extract. The comparative analysis of the pharmacokinetic parameters indicated that there were obvious differences between green tea extract administration and single substances administration.

Polyphenols in brewed green tea inhibit prostate tumor xenograft growth by localizing to the tumor and decreasing oxidative stress and angiogenesis

It has been demonstrated in various animal models that the oral administration of green tea (GT) extracts in drinking water can inhibit tumor growth, but the effects of brewed GT on factors promoting tumor growth, including oxidant damage of DNA and protein, angiogenesis and DNA methylation, have not been tested in an animal model. To explore these potential mechanisms, brewed GT was administered instead of drinking water to male severe combined immunodeficiency (SCID) mice with androgen-dependent human LAPC4 prostate cancer cell subcutaneous xenografts. Tumor volume was decreased significantly in mice consuming GT, and tumor size was significantly correlated with GT polyphenol (GTP) content in tumor tissue. There was a significant reduction in hypoxia-inducible factor 1-alpha and vascular endothelial growth factor protein expression. GT consumption significantly reduced oxidative DNA and protein damage in tumor tissue as determined by 8-hydroxydeoxyguanosine/deoxyguanosine ratio and protein carbonyl assay, respectively. Methylation is known to inhibit antioxidative enzymes such as glutathione S-transferase pi to permit reactive oxygen species promotion of tumor growth. GT inhibited tumor 5-cytosine DNA methyltransferase 1 mRNA and protein expression significantly, which may contribute to the inhibition of tumor growth by reactivation of antioxidative enzymes. This study advances our understanding of tumor growth inhibition by brewed GT in an animal model by demonstrating tissue localization of GTPs in correlation with inhibition of tumor growth. Our results suggest that the inhibition of tumor growth is due to GTP-mediated inhibition of oxidative stress and angiogenesis in the LAPC4 xenograft prostate tumor in SCID mice.

Polyphenol Content of Plasma and Litter after the Oral Administration of Green Tea and Tea Polyphenols in Chickens

Metabolic profiles of broiler chickens were examined after the ingestion of green tea, tea polyphenols, and (-)-epigallocatechin-3-gallate (EGCG). Solid-phase extraction of serum and litters yielded free catechins and their metabolites, which were then identified and quantified by liquid chromatography-tandem mass spectrometry. In plasma samples, (-)-gallocatechin, (+)-catechin, and EGCG were detected in the green tea group; pyrogallol acid, (epi)catechin-O-sulfate, 4'-O-methyl-(epi)gallocatechin-O-glucuronide, and (epi)catechin-3'-O-glucuronide were detected in the tea polyphenols group; and EGCG, (-)-gallocatechin gallate (GCG), and 4'-O-methyl-(epi)gallocatechin-O-glucuronides were detected in the EGCG group. In litters, gallic acid, EGCG, GCG, and ECG were detected in the green tea and tea polyphenols groups; EGCG and ECG were detected in the EGCG group. The conjugated metabolites, 4'-O-methyl-(epi)gallocatechin-O-glucuronide, (epi)catechin-3'-glucuronide, and 4'-O-methyl-(epi)catechin-O-sulfate, were identified in the green tea group; 4'-O-methyl-(epi)catechin-O-sulfate and 4'-O-methyl-(epi)gallocatechin-O-sulfate were identified in the tea polyphenols group; only 4'-O-methyl-(epi)gallocatechin-O-sulfate was detected in the EGCG group. The excretion of tea catechins was 95.8, 87.7, and 97.7% for the green tea, tea polyphenols, and EGCG groups, respectively.

Histological and biochemical markers of the liver of Wistar rats on subchronic oral administration of green tea

Background:Few articles have linked the consumption of green tea to certain liver diseases but several articles have disputed these assertions and the consumption of green tea has been on the increase.Aims:The effects of oral administration of green tea on the liver of Wistar rats were studied in order to compare biochemical findings with histological findings.Materials and Methods:36 male and female Wistar albino rats were grouped into 6, consisting of 6 rats in each group. They were given 1%, 2%, 3%, 4% and 5% concentration of green tea in tap water for 42 days. The 6th group was on normal diet and received 0% of the tea. Their blood samples were analyzed for total and conjugated bilirubin, total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The liver tissues were also processed for histological examination.Results:The liver tissues were essentially normal and similar to the control tissues. The biochemical parameters studied were also normal and similar to the results obtained from the control animals.Conclusion:Sub chronic consumption of green tea has no injurious effects on the liver of Wistar rats.

Positive effects of green tea on hepatic dysfunction, lipid peroxidation and antioxidant defence depletion induced by cadmium.

Cadmium (Cd) is a highly toxic environmental and industrial cumulative pollutant that affects many organs, especially the liver. The present study was designed to evaluate the antioxidant effect of green tea on cadmium-induced hepatic dysfunction and oxidative stress in rats. Adult male Wistar rats were administered cadmium by injection of 20 micromoles/kg bw/every 3 days for six months. This study revealed significant (p < 0.05) liver dysfunction, lipid peroxidation and a decline in antioxidant enzyme activities in the liver of cadmium-treated rats compared to control animals. Compared to control rats, the activities of lactate dehydrogenase (LDH), gammaglutamyl transferase (GGT), acid phosphatase (PAC), phosphatase alkaline (PAL), as well as bilirubin and thiobarbituric acid-reactive substances (TBARs), were significantly (p < 0.05) increased in Cd-treated rats. Moreover, antioxidant enzyme activities, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, were significantly (p < 0.05) decreased in the liver of cadmium-treated rats. The oral administration of 5% aqueous green tea extract, along with cadmium treatment for six months, caused a significant (p < 0.05) improvement in cadmium-induced toxicity by significantly decreasing (p < 0.05) the activities of enzymatic markers of liver dysfunction (LDH, GGT, PAC, PAL activities, as well as the bilirubin rate). Indeed, green tea extract significantly increased (p < 0.05) antioxidant enzymatic activities (SOD, Catalase, GPX) in rat liver, compared to those given cadmium alone. Thus, the oral administration of green tea, along with cadmium significantly (p < 0.05) improves cadmium-induced liver dysfunction and stress oxidant in rats' liver.

Some Natural Compounds EnhanceNɛ‐(Carboxymethyl)lysine Formation

Since pyridoxamine, which traps intermediates in the Maillard reaction and lipid peroxidation reaction, significantly inhibits the development of retinopathy and neuropathy in the streptozotocin‐induced diabetic rat, treatment with advanced glycation end product inhibitors and antioxidants may be a potential strategy for the prevention of clinical diabetic complications. However, the paradoxical effect of green tea has been reported; although plasma hydroperoxide levels were ameliorated, the level of Nɛ‐(carboxyethyl)lysine (CML) in tendon and plasma was increased by the oral administration of green tea to diabetic rats. In the present study, we measured the effect of natural compounds on CML formation by enzyme‐linked immunosorbent assay. A significant amount of CML was observed when bovine serum albumin was incubated with ribose for 7 days. Under the same conditions, natural compounds, such as desgalactotigonin, showed inhibitory effects, whereas quercetin and acteoside enhanced CML formation, indicating that natural compounds contain both inhibitors and enhancers for CML formation.

Effect of Caffeine on UVB‐induced Carcinogenesis, Apoptosis, and the Elimination of UVB‐induced Patches of p53 Mutant Epidermal Cells in SKH‐1 Mice†

Oral administration of green tea or caffeine to SKH-1 mice during UVB irradiation for several months inhibited the formation of skin cancer. Similar effects were observed when green tea or caffeine was given to tumor-free UVB-initiated mice with a high risk of developing skin tumors in the absence of further UVB irradiation (high risk mice). Mechanistic studies indicated that topical application of caffeine stimulated UVB-induced apoptosis as well as apoptosis in UVB-induced focal hyperplasia and tumors in tumor-bearing mice. Oral or topical administration of caffeine enhanced the removal of patches of epidermal cells with a mutant form of p53 protein that appeared early during the course of UVB-induced carcinogenesis, and oral administration of caffeine altered the profile of p53 mutations in the patches. In additional studies, topical application of caffeine was shown to have a sunscreen effect, and topical application of caffeine sodium benzoate was more active than caffeine as a sunscreen and for stimulating UVB-induced apoptosis. Caffeine sodium benzoate was also highly active in inhibiting carcinogenesis in UVB-pretreated high risk mice. Our studies indicate that caffeine and caffeine sodium benzoate may be useful as novel inhibitors of sunlight-induced skin cancer.

Effect of Green Tea on the mRNA Expression of Matrix Metalloproteinases in the Liver and Kidney of Diabetic Rats

Matrix metalloproteinases (MMPs) contribute to cardiovascular disease and are associated with vascular lesions in diabetes mellitus. In the present in vivo study, we investigated whether oral administration of green tea changes the mRNA expression of MMPs in diabetic rats, because green tea catechins inhibit mRNA expression and activity of MMPs in vitro. Experimental diabetes was induced in rats by a single injection of 50 mg / kg streptozotocin (STZ) into the tail vein. Diabetic rats were fed either a green tea-free diet (STZ rats) or a diet containing 5 % green tea (STZ + GT rats) for 4 weeks. Control rats are non-diabetic rats not treated with green tea. The mRNA expression of MMP-2, MN'IP-9, tissue inhibitor of metalloproteinases (TIMP) -1, TIMP-2, and TIMP-3 in rat liver and kidney was determined by real-time polymerase chain reaction. In the liver, there were no significant differences in the mRNA expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 between STZ rats and STZ + GT rats. However, TIMP-3 mRNA expression in the liver was significantly increased in STZ + GT rats compared with control and STZ rats. In the kidney, MMP-9 mRNA expression in STZ rats was significantly decreased compared with that in control rats, whereas that in STZ + GT rats recovered to levels the same as in control rats. MMP-2, TIMP-1, TIMP-2 and TIMP-3 mRNA expression in the kidney were significantly increased in STZ + GT rats compared with STZ rats. Thus, 5 % green tea treatment of STZ diabetic rats improved changes in the mRNA expression of MMPs and TIMPs in kidney tissue more efficiently than in the liver. The results of the present study suggest that the imbalance in the mRNA expression of MMPs and TIMPs in STZ diabetic rats is improved by green tea treatment.

Positive effects of Green Tea on hepatic dysfunction, lipid peroxidation and antioxidant defence depletion induced by cadmium

Cadmium (Cd) is a highly toxic environmental and industrial cumulative pollutant that affects many organs, especially the liver. The present study was designed to evaluate the antioxidant effect of green tea on cadmium-induced hepatic dysfunction and oxidative stress in rats. Adult male Wistar rats were administered cadmium by injection of 20 micromoles/kg bw/every 3 days for six months. This study revealed significant (p < 0.05) liver dysfunction, lipid peroxidation and a decline in antioxidant enzyme activities in the liver of cadmium-treated rats compared to control animals. Compared to control rats, the activities of lactate dehydrogenase (LDH), gammaglutamyl transferase (GGT), acid phosphatase (PAC), phosphatase alkaline (PAL), as well as bilirubin and thiobarbituric acid-reactive substances (TBARs), were significantly (p < 0.05) increased in Cd-treated rats. Moreover, antioxidant enzyme activities, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, were significantly (p < 0.05) decreased in the liver of cadmium-treated rats. The oral administration of 5% aqueous green tea extract, along with cadmium treatment for six months, caused a significant (p < 0.05) improvement in cadmium-induced toxicity by significantly decreasing (p < 0.05) the activities of enzymatic markers of liver dysfunction (LDH, GGT, PAC, PAL activities, as well as the bilirubin rate). Indeed, green tea extract significantly increased (p < 0.05) antioxidant enzymatic activities (SOD, Catalase, GPX) in rat liver, compared to those given cadmium alone. Thus, the oral administration of green tea, along with cadmium significantly (p < 0.05) improves cadmium-induced liver dysfunction and stress oxidant in rats' liver.

Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice

Earlier studies showed that oral administration of green tea or caffeine to SKH-1 mice inhibited ultraviolet B light (UVB)-induced skin carcinogenesis, decreased dermal fat thickness and increased locomotor activity. In the present study, the effects of voluntary running wheel exercise on thickness of dermal fat as well as on UVB-induced tumorigenesis in SKH-1 mice were studied in UVB-initiated high-risk and UVB-induced complete carcinogenesis models. In the high-risk model, animals were exposed to UVB (30 mJ/cm(2)) 3 times/week for 16 weeks. For 14 weeks subsequent to UVB exposure, half of the animals had access to running wheels in their cages whereas the other half did not. In the complete carcinogenesis model, animals were exposed to UVB (30 mJ/cm(2)) 2 times/week for 33 weeks. From the beginning, half of the animals had access to running wheels whereas the other half did not. At the conclusion of each study, body weights were not different between groups, although animals with running wheels consumed significantly more food and water than animals without running wheels. In addition, animals with running wheels had decreases in parametrial fat pad weight and thickness of the dermal fat layer. In both UVB-initiated high-risk and complete carcinogenesis models, voluntary running wheel exercise delayed the appearance of tumors, decreased the number of tumors per mouse and decreased tumor volume per mouse. Histopathology studies revealed that running wheel exercise decreased the number of non-malignant tumors (primarily keratoacanthomas) by 34% and total tumors per mouse by 32% in both models, and running wheel exercise decreased the formation of squamous cell carcinomas in the UVB-induced complete carcinogenesis model by 27%. In addition, the size of keratoacanthomas and squamous cell carcinomas were decreased substantially in both models. The effects described here indicate that voluntary running wheel exercise inhibits UVB-induced skin tumorigenesis and may also inhibit tumor growth.

Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma

The polyphenol epigallocatechin-3-gallate (EGCG), the principal mediator of the green tea, has been known to possess antitumor effect. The endothelin A receptor (ET(A)R)/endothelin-1 (ET-1) axis is overexpressed in ovarian carcinoma representing a novel therapeutic target. In this study, we examined the green tea and EGCG effects on two ovarian carcinoma cell lines, HEY and OVCA 433. EGCG inhibited ovarian cancer cell growth and induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3. Treatment with green tea or EGCG inhibited ET(A)R and ET-1 expression and reduced the basal and ET-1-induced cell proliferation and invasion. The EGCG-induced inhibitory effects were associated with a decrease of ET(A)R-dependent activation of the p42/p44 and p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase pathway. Remarkably, EGCG treatment resulted in a lowering of basal and ET-1-induced angiogenesis and invasiveness mediators, such as vascular endothelial growth factor and tumor proteinase activation. Finally, in HEY ovarian carcinoma xenografts, tumor growth was significantly inhibited by oral administration of green tea. This effect was associated with a reduction in ET-1, ET(A)R, and vascular endothelial growth factor expression, microvessel density, and proliferation index. These results provide a novel insight into the mechanism by which EGCG, affecting multiple ET(A)R-dependent pathways, may inhibit ovarian carcinoma growth, suggesting that EGCG may be useful in preventing and treating ovarian carcinoma in which ET(A)R activation by ET-1 plays a critical role in tumor growth and progression.

Oral administration of green tea epigallocatechin-3-gallate (EGCG) reduces amyloid beta deposition in transgenic mouse model of Alzheimer's disease

Oral administration of green tea epigallocatechin-3-gallate (EGCG) reduces amyloid beta deposition in transgenic mouse model of Alzheimer's disease