Sole Source Of Drinking Fluid Research Articles

Fermented Rooibos tea (Aspalathus linearis) Ameliorates Sodium Fluoride-Induced Cardiorenal Toxicity, Oxidative Stress, and Inflammation via Modulation of NF-κB/IκB/IκKB Signaling Pathway in Wistar Rats.

High dose of fluoride intake is associated with toxic effects on kidney and cardiac tissues. This study evaluated the potential protective effect of fermented rooibos tea (RTE) on sodium fluoride (NaF)-induced cardiorenal toxicity in rats. Male Wistar rats (n = 56) were randomly allocated into one of seven equal groups: control, NaF (100mg/kg orally), NaF + RTE (2%, w/v), NaF + RTE (4%, w/v), NaF + lisinopril (10mg/kg orally), 2% RTE, and 4% RTE. The experiment lasted for 14days and RTE was administered to the rats as their sole source of drinking fluid. NaF induced cardiorenal toxicity indicated by elevated level of urea, creatinine, LDH, creatinine kinase-MB, and cardiactroponin I in the serum, accompanied by altered histopathology of the kidney and heart. Furthermore, levels of H2O2, malondialdehyde, and NO were elevated, while GSH level was depleted in the kidney and heart due to NaF intoxication. Protein levels of c-reactive protein, TNFα, IL-1B, and NF-κB were increased by NaF in the serum, kidney, and heart. RTE at 2% and 4% (w/v) reversed cardiorenal toxicity, resolved histopathological impairment, attenuated oxidative stress and inhibited formation of pro-inflammatory markers. RTE at both concentrations down-regulates the mRNA expression of NF-κB, and upregulates the mRNA expression of both IκBand IκKB, thus blocking the activation of NF-κB signaling pathway. Taken together, these results clearly suggest that the protective potential of rooibos tea against NaF-induced cardiorenal toxicity, oxidative stress, and inflammation may be associated with the modulation of the NF-κB signaling pathway.

Mitigation of Colonic Inflammation in Dextran Sulfate Sodium-treated Mice by Dietary Supplementation with Soybean Fiber (P06-079-19)

ObjectivesSoybean fiber (SBF) is an insoluble, but highly fermentable dietary fiber. Previous in vitro fermentation studies with human feces have shown that SBF produces 1.5–8 times more acetate, propionate, and butyrate than oat bran, corn bran, or wheat bran fiber. Short chain fatty acids (SCFA) have been reported to play a key role in maintaining colon health and reducing inflammation. The impact of dietary SBF on colonic inflammation has not previously been examined. Our objective was to determine the anti-inflammatory efficacy of dietary supplementation with SBF in a mouse model of acute colonic inflammation. MethodsMale C57BL/6 J mice (5 weeks old) were randomized to AIN93G diet (CTL) or diet where 40% of the fiber was replaced with SBF (SBF-Hi). After 2 weeks of pretreatment, mice were given 2% dextran sulfate sodium (DSS) as the sole source of drinking fluid for 1 week to induce colonic inflammation. During DSS treatment, mice were maintained on their diet treatments. After DSS treatment, mice were euthanized and colonic inflammation was assessed. ResultsDSS-treated mice had significantly larger spleens and shorter colons than mice treated with water. SBF-Hi mitigated DSS-induced increases in spleen weight (20% lower) and colon shortening (15% longer). Quantitative, reverse transcriptase PCR analysis showed that DSS-treatment increased colonic mRNA expression of interleukin-6 (Il6) and tumor necrosis factor-a (Tnfa) by 3-fold compared to water-treated mice. Dietary supplementation with SBF blunted these increases in Il6 and Tnfa by 87% and 71%, respectively. ConclusionsOur results suggest that dietary supplementation with SBF may be a useful approach to mitigate colonic inflammation. On-going studies are focused on determining fecal levels of SCFA and measuring protein markers of inflammation and gut barrier function. Future studies are needed to evaluate whether the protective effects observed in this study are maintained in situations of more chronic colonic inflammation. Funding SourcesThis work was funded by a grant from the Pennsylvania Soybean Board and by USDA National Institute of Food and Agriculture Appropriations under Project PEN04565.

Comparative effect of black, green, oolong, and white tea intake on weight gain and bile acid metabolism.

The beneficial effects of tea on health, including obesity, are well known. However, the comparative effects of black, green, white, and oolong teas, which are prepared from the same fresh leaves, on weight gain and the potential mechanisms involved are not yet fully understood. Bile acids (BAs) are shown to be powerful regulators of metabolism; however, to our knowledge, no studies have investigated the effect of tea on BA metabolism. The aim of this study was to investigate the modulatory effects that green, black, white, and oolong teas that were prepared from the same raw tea leaves have on the plasma BA profile. Female rats were dosed with the aforementioned tea types as their sole source of drinking fluid for 28 d. We then investigated their weight and effect on BA metabolic profile using advanced ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS)-based metabolomics. The UPLC-MS/MS analysis of the plasma show that the levels of murocholic acid, glycochenodeoxycholic acid, glycocholic acid, glycodeoxycholic acid, taurochenodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid, tauromuricholic acid, and taurocholic acid were increased; whereas levels of taurolithocholic acid and isolithocholic acid were decreased after drinking green, oolong, and white tea types compared with control. Surprisingly, oolong tea significantly influenced reduction in relative weight compared with control, black, and green tea; whereas black, green, and white teas had no effects on weight compared with control. Green, black, oolong, and white teas altered the BA metabolism. This change in BA metabolism could be associated with the health benefit effects of tea. Oolong tea was most effective in reducing weight.

(-)-Epigallocatechin-3-gallate decreases colonic inflammation and permeability in a mouse model of colitis, but reduces macronutrient digestion and exacerbates weight loss.

(-)-Epigallocatechin-3-gallate (EGCG) has been reported to have putative health effects including the prevention of inflammation and obesity. Historically, polyphenols have been regarded as antinutritionals and while such effects may be beneficial in obese subjects, they may be deleterious in nutritionally compromised individuals. We examined the effect of EGCG in the dextran sulfate sodium (DSS)-treated mouse model of ulcerative colitis. Following induction of colitis, mice were treated with EGCG (3.2 mg/g) as the sole source of drinking fluid for 3 days. EGCG treatment mitigated DSS-induced colon shortening and spleen enlargement. EGCG also decreased colonic protein levels of IL-1β, IL-6, and tumor necrosis factor-α, as well as colonic lipid peroxides compared to DSS-treated controls. We observed that EGCG reduced DSS-induced gastrointestinal permeability. These beneficial effects were offset by enhanced body weight loss in EGCG-treated mice compared to DSS-treated controls. These effects were related to decreased protein and lipid digestion in EGCG-treated mice compared to DSS-treated controls. Our results suggest that although EGCG may exert anti-inflammatory effects, its ability to modulate macronutrient digestion may represent a dose-limiting adverse effect that must be considered in the context of its use for treating inflammatory bowel disease.

Ultrastructural Changes in Cerebral Histaminergic Neurons on Exposure to Alcohol

The aim of the present work was to analyze the ultrastructural changes developing in cerebral histaminergic neurons in 24 mongrel white male rats after administration of ethanol in acute experimental conditions (single i.p. doses of 1 and 4 g/kg), in subacute conditions (sole source of drinking fluid, 4 g/kg, for 7 days), or chronic conditions (2–3 g/kg/day for 6 months). Administration of alcohol led to the development of a variety of ultrastructural changes in the nuclei and organelles of histaminergic neurons. These reflect neuron destruction processes and adaptive changes directed at restoring and maintaining cell functions. These changes were nonspecific in nature and depended on dose, time after administration, and duration of treatment; overall, they corresponded to structural and histochemical changes detected at the light microscope level.

(‐)‐Epigallocatechin 3‐gallate decreases markers of inflammation in a mouse model of ulcerative colitis (1045.24)

Ulcerative colitis (UC) is an inflammatory bowel disease that manifests as constant/cyclic episodes of colonic inflammation, oxidative stress, increased intestinal permeability, and ulceration followed by periods of quiescence. UC increases risk of colon cancer. Green tea polyphenols, such as epigallocatechin‐3‐gallate (EGCG), have been shown to inhibit oxidative stress in animal and cell studies. Here, we examined the anti‐inflammatory effects of EGCG in the dextran sulfate sodium (DSS)‐induced CF‐1 mouse model of UC. Following induction of colitis by treatment with 1.5% DSS for 7 days, mice were treated with EGCG (0.32%) as the sole source of drinking fluid for 3 days. In the colon homogenate, inflammatory cytokine levels of IL‐6 and TNF‐α were decreased by 50% and IL‐1β by 25% as a result of the EGCG administration. Plasma inflammatory markers and endotoxin levels were also decreased. These results suggest that EGCG can decrease both inflammatory response and intestinal permeability in the DSS‐induced UC mouse model. Ongoing mechanistic studies are focused on determining the effect of EGCG on gut barrier function.

Chemopreventive efficacy of green tea drinking against 1,2‐dimethyl hydrazine‐induced rat colon carcinogenesis

Colorectal cancer is one of the leading causes of tumour-related deaths. In the present study, the chemopreventive effect of green tea on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied in male Wistar rats. The DMH group received subcutaneous injections of DMH (30 mg kg(-1) body weight) once a week for 30 weeks, the normal group received the vehicle of DMH, and the DMH + green tea group received DMH simultaneously with 1% green tea as their sole source of drinking fluid throughout the experimental period. In the DMH group treated with green tea, significant reductions in gene overexpressions of colonic nuclear factor κB (NF-κB), tumour necrosis factor α, inducible nitric oxide synthase and cyclooxygenase 2, and NF-κB immunostaining indicates the anti-inflammatory effect of green tea in attenuating colon cancer. Moreover, the anti-angiogenic and anti-invasiveness effects of green tea were revealed as reductions of both vascular endothelial growth factor and matrix metalloproteinase-7 mRNA expression levels. These effects were confirmed by the significant reduction of serum tumour necrosis factor α, C-reactive protein levels, inhibition of tumour incidence, and nearly normal survival rate and colonic architecture. It can be concluded that green tea exerts a potent chemopreventive effect on colon carcinogenesis possibly due to the inhibition of NF-κB.

Abstract 840: Pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP mouse model

Abstract Pomegranate fruit extract (PFE) dubbed as “nature's power fruit” was found to prolong prostate specific antigen (PSA) doubling time in men with rising PSA after surgery and therapy and hailed as a promising non-toxic strategy for slowing the progression of prostate cancer (PCa). To ascertain conclusive evidence of the effects of PFE against PCa require its efficacy evaluation in animal models that closely emulate human disease. Here, we provide evidence of remarkable tumor growth inhibitory effects using TRAMP, an autochthonous transgenic mouse model that mimics progressive forms of human PCa. Mice were supplied with 0.1% and 0.2% PFE as the sole source of drinking fluid starting at the age of 6 weeks. This drinking regimen is based on the assumption that a typical healthy individual (70 kg) may be persuaded to drink 250 or 500 ml of PFE from one or two fruits, respectively. Animals were examined at 12, 20 and 34 weeks of age for prostate tumor growth. In water-fed group, 100% mice developed palpable tumors by 20 weeks of age compared to only 30% and 20% in the 0.1% and 0.2% PFE-fed groups, respectively as assessed by abdominal pelvic palpation, MRI and ultrasound based imaging. At 34 weeks of age palpable tumors were observed in 70% of 0.1% PFE fed and only 50% of 0.2% PFE-fed TRAMP mice. Compared to a median survival of 43 weeks in water-fed mice, PFE-fed mice exhibited significant increase in life span with 0.1% and 0.2% PFE-fed mice exhibiting median life expectancy of 73 and 92 weeks, respectively. The cumulative data on metastasis at 20 and 34 weeks of age in the water-fed group showed 30% and 90% incidence of invasive tumors, which had metastasized to the lungs and liver. In sharp contrast, in the 0.1% and 0.2% PFE-fed group, none of the 20 mice exhibited metastases to any of the distant organs studied at 20 weeks of age and only 20% mice exhibited metastasis at 34 weeks of age. PFE feeding resulted in significant decrease in hyperplasia in the genitourinary (GU) apparatus, especially in the seminal vesicles. A significant decrease in GU weight (∼68% in 0.1% PFE and ∼79% in 0.2% PFE) compared with the water-fed TRAMP group was observed. At 34 weeks of age prostates of PFE-fed TRAMP mice contained well-differentiated adenocarcinoma that occupied ∼20% at surface area, admixed with lesser amounts of moderately differentiated adenocarcinoma (<3% of surface area), histology that was comparable to controls at 12 weeks of age. Many of the PFE-fed animals had multiple foci of well differentiated carcinoma (10-20% of surface area) and some had poorly differentiated carcinoma. PFE feeding resulted in simultaneous and significant inhibition of the IGF-I/Akt/mTOR pathways in the prostate tissues and tumors. This is significant since such a combined inhibition is seen only with a combination of drugs and not with a single agent alone. We suggest that pomegranate juice be evaluated in clinical trials in patients at high risk for developing prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 840. doi:10.1158/1538-7445.AM2011-840

Abstract 1894: Cocoa tea (Camellia ptilophylla): another beverage for chemotherapy of prostate cancer

Abstract Prostate cancer (PCa) is the most common malignancy and the second leading cause of male death in USA and many European countries. It is therefore necessary to intensify our efforts to better understand this disease and develop novel approaches for its prevention and treatment. One approach to control PCa is its prevention through agents present in diet and beverages consumed by humans. Almost all supplements sold to the consumer with the promise of improving prostate health contain antioxidants. One such agent which has received much attention for prevention and treatment of PCa is green tea, whose effects are attributed to polyphenols present therein. Cocoa tea derived from the plant Camellia ptilophylla is a natural decaffeinated tea plant which grows in southern China. The local people have habitually drunk cocoa tea for a long time, not only as a healthy beverage but also as a traditional remedy for ailments. Herein, we provide evidence that cocoa tea also possesses strong antioxidant properties and could be useful for prevention and treatment of PCa. We extracted white cocoa tea, green cocoa tea and black cocoa tea with water and their extracts are referred to as WCT, GCT and BCT, respectively. Based on HPLC analysis, WCT and GCT were found to mainly contain four catechins including gallocatechin gallate, epigallocatechin gallate, catechin, gallocatechin and theobromine. No caffeine was detected in WCT, GCT and BCT. Besides, WCT contained more catechins than GCT and BCT. MTT assay showed that among the three extracts, WCT had the strongest inhibition of cell growth in PC-3 cells. Treatment of PC-3 cells with WCT (100-150 µg/ml, equivalent GCG 44-66 µM;72 h) inhibited cell proliferation which correlated with G2/M phase cell cycle arrest. Immunoblot analysis revealed that WCT treatment to PC3 cells resulted in, (i) induction of WAF1/p21 and KIP1/p27; (ii) decrease in cyclins D1, D2 and E; (iii) decrease in cyclin-dependent kinase (cdk) 2, 4 and 6; (iv) induction of Bax and downregulation of Bcl-2; (v) decrease in procaspase-3, −8; (vi) inhibition of nuclear translocation and phosphorylation of NF-κB, and activation of IKKα; (vii) inhibition of phosphorylation and degradation of IκBα. Next, athymic nude mice (6-8 weeks old) were implanted with PC-3 cells and divided into three groups. Treated group of animals received freshly prepared solution of 0.1% and 0.2% WCT in drinking water as the sole source of drinking fluid throughout the experiment. The animals were followed for tumor growth twice weekly. Compared to that in water fed mice, considerably slower tumor growth (P<0.01) was observed in animals receiving WCT as compared to those receiving water. There was significant increase in p21, Bax/Bcl2 protein ratio, and the inhibition of cyclin D1, p-NF-κB/p65 protein levels in tumors of mice treated with WCT. We suggest that cocoa tea may also possess cancer chemotherapeutic effects against PCa in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1894.

Influence of vitamin E on alcohol-induced changes in antioxidant defenses in mice liver

It is widely accepted that oxidative stress plays a central role in alcohol-induced pathogenesis. Redox-sensitive transcription factors nuclear factor-κB (NFκB) and activator protein-1 (AP1) are involved in development of alcohol-related diseases. Because of its antioxidative properties, vitamin E is believed to prevent diseases associated with oxidative stress. The aim of the present study was to evaluate the molecular mechanism associated with alcohol-induced oxidative stress and its prevention with vitamin E supplementation. Male Balb/c mice were divided into three groups viz. group I (control), group II (alcohol-treated) and group III (alcohol-treated + Vitamin E supplemented). Group II received 8% alcohol as sole source of drinking fluid while group III was given Vitamin E orally as 5 IU/kg body weight along with 8% alcohol. After 15 days, increases in lipid peroxidation, catalase and GST activity and decreases in SOD activity as well as redox ratio were observed in group II. This was associated with increased apoptosis in this group. Vitamin E supplementation restored the redox status, reduced apoptosis and prevented oxidative stress. Further mRNA expression of cjun, cfos, p65 (NFκB) showed increased expression during oxidative stress in group II. Although inhibition in NFκB activation was observed with Vitamin E, on the contrary it stimulated AP1 expression. This study supports the fact that alcohol promoted oxidative stress and is the major cause of alcohol toxicity in liver. Vitamin E can mitigate the toxic effects of alcohol and can be suitably used as a potential therapeutic agent for alcohol-induced oxidative damage in liver.

Syndecan-1 expression and its significance in colitis

To explore the effect of syndecan-1 (Sdc-1) in the pathogenesis of colitis. Thirty BALB/c mice were forced to drink 4% dextran sodium sulphate (DSS) in distilled water as the sole source of drinking fluid for 7 days, distilled water for 10 days, and 4% DSS in distilled water for another 7 days so as to establish colitis models and then were randomly divided into 3 equal groups: model groups 1, 2, and 3 to be killed 8, 18, and 25 days after the DSS drinking respectively to take their colons. Another 10 mice were fed with distilled water as control group and were killed on Day 8. Microscopy was used to evaluate the histological score of the colon. RT-PCR was used to detect the expression of Sdc-1 mRNA and IL-1 mRNA in the colon mucosa. Immunohistochemistry was conducted to detect the Sdc-1 protein level. The histological scores of the 3 model groups were all significantly higher than that of the control group (F = 448.717, P < 0.01) and the score was the highest in the model group 1 and then gradually decreased. There was not significant differences in the Sdc-1 mRNA expression among different groups (F = 0.822, P > 0.05). The levels of Sdc-1 protein of the 3 model groups were all significantly lower than that of the control group (F = 865.586, P < 0.01), and the Sdc-1 protein level was the lowest level in the model group1, and then increased gradually. The expression of IL-1 mRNA of the 3 model groups were all significantly higher than that of the control group (F = 103.833, P < 0.01), and the IL-1 mRNA level was the highest in the model group1 and then decreased gradually. The severity of colitis is associated with the reduction of Sdc-1 protein level, but not with the Sdc-1 mRNA level in the colon mucosa. The reduction of Sdc-1 protein level may be associated to increase of IL-1 level.

Comparison of White Tea, Green Tea, Epigallocatechin-3-Gallate, and Caffeine as Inhibitors of PhIP-Induced Colonic Aberrant Crypts

: There is growing interest in the possible health benefits of tea. We reported previously on the inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypt foci (ACF) in the rat (4). To distinguish between blocking and suppressing effects, and thus provide mechanistic insights into prevention during the initiation versus post-initiation phases of carcinogenesis, white tea, and green tea were administered at 2% (w/v) as the sole source of drinking fluid either 2 wk before and 2 wk during PhIP dosing (100 mg/kg, every other day by oral gavage), or starting 1 wk after the carcinogen and continued until the study was terminated at 16 wk. In the former protocol, each tea produced marginal inhibition of colonic ACF, despite evidence for changes in several hepatic enzymes involved in heterocyclic amine metabolism. Post-initiation, however, the data were as follows (ACF/colon, mean ± SE): PhIP/water 12.2 ± 1.5; PhIP/white tea 5.9 ± 0.9 (** P < 0.01); PhIP/caffeine 5.9 ± 1.5 (** P < 0.01); PhIP/EGCG 3.5 ± 0.8 (***P < 0.001); PhIP/green tea 8.9 ± 1.2 (P = 0.22, not significant). In the latter study, apoptosis was determined using in situ oligo ligation and cleaved caspase-3 assays, whereas cell proliferation was assessed via bromodeoxyuridine (BrdU) incorporation. No consistent changes were seen in apoptosis assays, but BrdU labeling was as follows (percent of cells positive/colonic crypt, mean ± SE): PhIP/water 10.4 ± 0.6; PhIP/white tea 8.6 ± 0.2 (*P < 0.05); PhIP/EGCG 6.0 ± 0.85 (** P < 0.01); PhIP/caffeine 8.75 ± 0.45 (*P < 0.05); PhIP/green tea 9.5 ± 0.4 (P > 0.05, not significant). The data imply that white tea, caffeine, and EGCG may be most effective post-initiation, via the inhibition of cell proliferation in the colon and through the suppression of early lesions.

Estrogen protects aldosterone/NaCl‐induced hypertension in conscious rats

Previous studies from our laboratory have shown that there are sex differences in the development of aldosterone (ALDO)/NaCl-induced hypertension. The present study was performed to determine which sex hormone is responsible for these sex differences. Male and female Sprague-Dawley rats were infused subcutaneously with ALDO (0.75 μg/h, 28 days) and 1% NaCl was provided as the sole source of drinking fluid. Aortic blood pressure was measured by DSI® telemetry. ALDO+1% NaCl-treated male rats progressively developed hypertension (101.6±2.8 to 124.6±3.6, Δ23.2±3.7 mmHg, n=6) but blood pressures in females were not different from the control values (98.4±1.7 to 101.8±3.5, Δ3.4±1.4 mmHg, n=4). Gonadectomy augmented ALDO+1% NaCl-induced hypertension in females (Δ17.1±2.3 mmHg, n=3) but had no effect in males (Δ20.9±2.2 mmHg, n=4). Moreover, systemic infusion of 17β-estradiol (250 μg/day) totally blocked ALDO+1% NaCl-induced hypertension in intact males (Δ-1.5±2.4 mmHg, n=3). These results indicate that estrogen may play a protective role in the development of ALDO+1% NaCl-induced hypertension. (Supported by NIH HL-59676, HL-62261, HL-14388, and DK-66086.)

Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine

The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.

Sex difference in Aldosterone/Salt‐induced hypertension in conscious rats

Many studies have focused on the role of aldosterone (Aldo) and NaCl in the pathophysiology of hypertension. However, few studies have investigated sex differences in Aldo/salt-induced hypertension. The purpose of the present study was to test the hypothesis that male and female Sprague-Dawley rats respond differently to subcutaneous infusion of Aldo (0.75 μg/h) combined with 1% NaCl as the sole source of drinking fluid. Aortic blood pressure (BP) and heart rate (HR) was measured in conscious, freely moving rats with the use of telemetry implants. Resting BP in males and females were not different (101.6±1.5, n=3 vs 98.5±3.2 mmHg, n=3), but resting HR tended to be higher in the females (401.9±3.5 bpm) than the males (375.6±2.7 bpm). Neither subcutaneous infusion of Aldo alone (14 days, n=3) nor presenting 1% NaCl as the drinking fluid alone (14 days, n=2) changed the basal blood pressure in males or females. However, following placement of rats on both Aldo and 1% NaCl for 14 days, the resting BP in the males increased by 17±4.5 mmHg, but the BP in females was not different from the control values (103.6±0.7 mmHg). HR was reduced in both males (297.4±2 bpm) and females (338.9±4.7 bpm). The data indicates that female rats are protected from Aldo/Salt-induced hypertension. (Supported by NIH Grant 62261 and 59676)

Protective effects of black tea extract on testosterone induced oxidative damage in prostate

Since ancient times, antipyretic, anti-inflammatory, antimicrobial and antioxidative properties of tea have been recognized. Black tea ( Camellia sinensis) contains a variety of polyphenolic ingredients including the theaflavins (TF), thearubigins (TG) and catechins. Components from black tea have been accounted to play an important role in scavenging free radicals generated by mutagens and carcinogens. Androgens are the key factors in either the initiation or progression of prostate cancer (PCA) by inducing oxidative stress. In the present set of investigations, the antioxidative potential of black tea extract against androgen mediated oxidative stress in male Wistar rats has been studied. Testosterone was given at a dose of 5 mg/kg b.w. subcutaneously, consecutively for 5 days. Prior to androgen administration, animals were kept on 0.5, 1.0 and 1.5% aqueous tea extract (ATE) as sole source of drinking fluid for 15 days. The prostate tissue was dissected out for biochemical analysis for antioxidant enzymes viz. catalase (CAT), superoxide dismutase (SOD), lipid peroxidation (LPO), glutathione- s-transferase (GST) and glutathione reductase (GR). The results revealed that testosterone administration induced the oxidative stress in rat prostate, however, in 0.5, 1.0 and 1.5% ATE supplemented groups, a significant protective effect of black tea against testosterone induced oxidative injury was recorded. Hence, the study reveals that constituents present in black tea impart protection against androgen induced oxidative injury that may result in development of prostate cancer.

Administration of green tea or caffeine enhances the disappearance of UVB-induced patches of mutant p53 positive epidermal cells in SKH-1 mice

Irradiation of female SKH-1 hairless mice with UVB (30 mJ/cm2) twice a week for 10-20 weeks resulted in the formation of a large number of cellular patches (>8 adjacent cells/patch) that are recognized with an antibody (Pab240) which recognizes mutated but not wild-type p53 protein. These patches are not recognized by an antibody (Pab1620) to wild-type p53 protein. The patches, which are considered putative early cellular markers of the beginning of tumor formation, started appearing after 4-6 weeks of UVB treatment, and multiple patches were observed after treatment for 10 weeks. The number and size of the patches increased progressively with continued UVB treatment. Discontinuation of UVB for 4 weeks resulted in an 80-90% decrease in the number of these patches. The number of the remaining patches did not decrease any further but remained relatively constant for at least 4-9 weeks. Oral administration of green tea (6 mg tea solids/ml) or caffeine (0.4 mg/ml) as the sole source of drinking fluid during irradiation with UVB, twice a week for 20 weeks, inhibited UVB-induced formation of mutant p53 positive patches by approximately 40%. Oral administration of green tea (6 mg tea solids/ml) as the sole source of drinking fluid or topical applications of caffeine (6.2 micromol) once a day 5 days a week starting immediately after discontinuation of UVB treatment enhanced the rate and extent of disappearance of the mutant p53-positive patches. Topical applications of caffeine to the dorsal skin of mice pretreated with UVB for 20 weeks resulted in enhanced apoptosis selectively in focal basal cell hyperplastic areas of the epidermis (putative precancerous lesions), but not in areas of the epidermis that only had diffuse hyperplasia. Our studies indicate that the chemopreventive effect of caffeine or green tea may occur by a proapoptotic effect preferentially in early precancerous lesions.

Prognostic Significance of Metastasis-Associated Protein S100A4 (Mts1) in Prostate Cancer Progression and Chemoprevention Regimens in an Autochthonous Mouse Model

We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.

Ex vivo modulation of chemical-induced mutagenesis by subcellular liver fractions of rats treated with rooibos ( Aspalathus linearis) tea, honeybush ( Cyclopia intermedia) tea, as well as green and black ( Camellia sinensis) teas

Male Fischer rats were given unprocessed (not oxidized) and processed (oxidized) rooibos and honeybush teas as well as green and black teas as a sole source of drinking fluid for 10 weeks, and sub cellular liver fractions were prepared. Cytosolic fractions of rats consuming the unprocessed herbal teas, green and black teas significantly ( P<0.05) protected against 2-acetylaminofluorene (2-AAF)-induced mutagenesis in the Salmonella mutagenicity test with strain TA 98, using Aroclor 1254-induced microsomes. A marginal or no protection was obtained with the processed herbal teas. The mutagenic response of aflatoxin B 1 (AFB 1) against Salmonella strain TA 100 was significantly ( P<0.05) inhibited by cytosolic fractions from rats treated with processed and unprocessed herbal teas, while no effect was obtained with the green and black teas. Microsomal fractions prepared from livers of rats treated with both the processed and unprocessed rooibos teas and the unprocessed honeybush tea, significantly ( P<0.05) reduced the activation of AFB 1 while no protection was observed against 2-AAF-induced mutagenesis. In contrast, microsomal fractions from rats treated with the green, black and unprocessed honeybush teas significantly ( P<0.05) enhanced the mutagenic response of 2-AAF. None of the tea treatments significantly affected the concentration of the microsomal liver cytochrome P450.

Inhibition of Lung Carcinogenesis and Effects on Angiogenesisand Apoptosis in A/J Mice by Oral Administration of Green Tea

Oral administration of tea (Camellia sinensis) has been shown to inhibit the formation and growth of several tumor types in animal models. The present study investigated the effects of treatment with different concentrations of green tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Two days after a single dose of NNK (100 mg/kg body weight, i.p.), the mice were given 0.1, 0.2, 0.4, and 0.6% green tea solution (1, 2, 4, and 6 g of tea solids, respectively, dissolved in 1 l of water), 0.02% caffeine, or water as the sole source of drinking fluid until the termination of the experiment. Only the treatment with 0.6% tea preparation significantly reduced lung tumor multiplicity (mean ± SE, 6.07 ± 0.77 vs. 8.60 ± 0.50 tumors per mouse, P = 0.018). Treatment with 0.6% tea also inhibited angiogenesis, as indicated by the lower microvessel density (number of blood vessels/mm2) based on immunostaining for the von Willebrand factor antigen (81.9 ± 9.5 vs. 129.4 ± 8.2, P = 0.0018) and anti-CD31 antibody staining (465.3 ± 61.4 vs. 657.1 ± 43.6, P = 0.0012). Significantly lower vascular endothelial growth factor immunostaining scores were also observed in the 0.6% tea-treated group (0.98 ± 0.17 vs. 1.43 ± 0.07, P = 0.006). The apoptosis index was significantly higher in lung adenomas from 0.6% tea-treated mice based on morphological analysis of cell apoptosis (2.51 ± 0.18% vs. 1.57 ± 0.11%, P = 0.00005), and the result was further confirmed using the TUNEL method. Inhibition of angiogenesis and the induction of apoptosis by green tea may be closely related to the inhibition of pulmonary carcinogenesis.