Protective Effects Of Tea Polyphenols Research Articles

Tea polyphenols protect bovine intestinal epithelial cells from the adverse effects of heat-stress in vitro

Heat-stress (HS) leads to impaired gut health, adversely affecting milk production of dairy cows. In the present study, we investigated the protective effects of tea polyphenols (TP) against HS-induced damage in bovine intestinal epithelial cells (BIECs) and explored the underlying mechanisms. Primary BIECs were isolated from bovine duodenum, cultured and treated as follows: (1) control cells incubated in complete medium at 37 °C for 12 h, (2) TP group incubated in medium containing 100 μg/mL TP at 37 °C for 12 h, (3) HS group incubated in medium at 37 °C for 6 h followed by 6 h at 42 °C, and (4) HS + TP group incubated with 100 μg/mL TP for 6 h at 37 °C and 6 h at 42 °C. TP improved cell viability and antioxidant capacity, and decreased apoptosis and LDH activity. TP led to upregulation of Nrf2 and its target antioxidant genes HO-1, NQO1 and SOD1 expression. TP significantly decreased the expression of proinflammatory cytokine genes (NF-κB, IL-6 and TNF-α), and increased expression of the anti-inflammatory cytokine gene, IL-10. The above results suggested that TP protected BIECs from HS-induced adverse effects by alleviating oxidative stress and inflammatory responses, indicating that TP can alleviate HS-induced intestinal damage in dairy cows.

Protective mechanism of tea polyphenols against muscle quality deterioration of shrimp (Penaeus vannamei) induced by aflatoxin B1

Tea polyphenols (TP), as common antioxidants, have been widely used to mitigate for the protection and preservation of aquatic animals, but the protective effect of TP against the deterioration of shrimp muscle quality induced by aflatoxin B1 (AFB1) has not been reported. This study was designed to analyse the root cause of AFB1 induced declines in shrimp muscle quality and the protective mechanisms of TP at the molecular level. Shrimp were exposed to AFB1 and TP for 20 d following a dose-escalating trial, and changes to the muscle histopathology, basic nutrient composition, and protein composition were determined. Non-labelled quantitative proteomics was used to screen and identify differential marker proteins associated with AFB1 and TP. After 20 d of AFB1 exposure, the water content, crude protein content and crude fat content of the shrimp muscle decreased to 68.66%, 18.27% and 1.01%, respectively, while the ash content was positively correlated with AFB1 dose (R2 = 0.955). AFB1 caused damage to the shrimp muscle microstructure in a dose-dependent manner, such as significant enlargement of muscle fibre spaces, rupture of the sarcomere, inflammation and so on. AFB1 induced changes in muscle protein composition, resulting in a decrease in the content of myofibrillar, sarcoplasmic and stroma proteins, while the alkali-soluble protein content increased significantly. TP can effectively protect against the damage to shrimp muscle caused by AFB1 by inhibiting the expansion of muscle fibre spaces and inflammation. TP (0.04–0.16% feed) also had a significant protective effect against the decrease of muscle nutrients and changes in protein composition of shrimp caused by exposure to AFB1 (1.2–2.7 mg/kg feed) in the early and middle period (4–12 d), but the protective effect was weak or not noticeable in the late period (16–20 d). Eleven proteins were identified and screened as biomarker proteins of AFB1 induced quality decline and TP protection, which were involved in energy metabolism (fructose 1,6-bisphosphatase; transaldolase; fructose-bisphosphate aldolase; arginine kinase), redox reaction (hydroxyphenylpyruvate reductase; prostaglandin reductase 1; protein arginine N-methyltransferase 8), anti-inflammatory responses (5′-nucleotidase; actin-depolymerizing factor) and protein translation/folding (eukaryotic translation initiation factor 3; peptidyl-prolyl cis-trans isomerase). This study provides a better understanding of AFB1 induced damage to shrimp quality and technical guidance for the use of TP to prevent the damage during the culture and processing of Penaeus vannamei.

Tea polyphenols protect learning and memory in sleep-deprived mice by promoting AMPA receptor internalization.

Chronic sleep loss caused lots of health problems, also including cognition impairment. Tea is one of the most popular drinks when people stay up late. Nevertheless, the effects of tea on sleep deprivation-induced cognition impairment are still unclear. In the present study, we found 24-h sleep deprivation (S-DEP) increased membrane α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor level through a tumor necrosis factor α (TNFα)-dependent pathway in hippocampi. Blocking elevated TNFα level can protect S-DEP mice from impaired learning ability according to behavioral test. Tea polyphenols, major active compounds in green tea, suppressed TNFα production through downregulating TNFα converting enzyme (TACE) level. Meanwhile, tea polyphenols treatment could ameliorate recognition impairment and anxiety-like behaviors in S-DEP mice. The aforementioned results demonstrate cognition protective effects of tea polyphenols in S-DEP mice model, which provide a theoretical basis for the treatments of S-DEP-induced cognition impairment by targeting the TACE/TNFα/AMPA pathway.

Nuclear magnetic resonance-based plasma metabolomics revealed the protective effect of tea polyphenols on sulfur mustard-induced injury in rats

Tea polyphenols (TP) are the major antioxidant components from tea, which could be beneficial to oxidative stress injury, such as sulfur mustard (SM) exposure. However, the holistic efficacy of TP on SM poisoning remains unexplored and needs further investigation. In this study, Nuclear magnetic resonance(NMR)-based metabolomics along with multivariate statistical analysis was used to explore the metabolic alteration after SM injury and the protective mechanism of TP. Thirteen potential plasma biomarkers of SM injury were identified, which primarily related to synthesis of ketone bodies, arginine and proline metabolism, butanoate metabolism and alanine aspartate and glutamate metabolism. After TP pre-treatment, the biomarkers were mostly restored to normal levels, which suggested that TP provided effective protection against SM injury and might play its role by rebalancing disordered metabolism pathways. This work enhanced our comprehension of the metabolic profiling of SM injury and revealed the protective mechanism of TP.

The protective effect of tea polyphenols on chronic alcoholic liver injury in rats

To investigate the protective effects and potential mechanisms of tea polyphenols intervention on excess alcohol intake induced liver injury in rats. This study established the animal model of chronic liver injury rats induced by alcohol. Our results will provide experimental evidence for the effects of tea polyphenol on chronic alcoholic liver injury. Alcohol-induced liver injury rat models were established, and the tea polyphenols intervention was performed in the meantime. After 8 weeks, rats were anesthetized, and visceral fat and liver samples were separated, weighted and stored. Visceral fat content was evaluated in fat/body weight ratio. Liver lipid accumulation was assessed by liver index and the result of Oil Red O staining. Hepatic superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant capacity assay (T-AOC) and glutathione peroxidase (GSH-Px) activity were detected. And fatty acid translocase (FAT/CD36) protein level in liver was detected. Compared with the control group rats, the fat/body weight ratio, SOD/MDA, T-AOC and GSH-Px activity of chronic liver injury rats were decreased significantly (P<0.05,P<0.01). Meanwhile the liver index, FAT/CD36 protein level and lipid deposition in liver of chronic liver injury rats were increased (P<0.01). Compared with chronic liver injury rats, the tea polyphenols intervention increased fat/body weight ratio (P<0.05), and significantly increased SOD/MDA, T-AOC and GSH-Px activity (P<0.01). Meanwhile the tea polyphenols intervention reduced liver index (P<0.01), FAT/CD36 protein level (P<0.01) and lipid deposition in liver. Tea polyphenols intervention can improve lipid deposition and oxidative stress in chronic alcoholic liver, which is concurrent with decreased FAT/CD36 protein expression on the hepatocyte membrane.

Protective effects of tea polyphenols and \u03b2-carotene against \u03b3-radiation induced mutation and oxidative stress in Drosophila melanogaster

BackgroundThe commonly consumed antioxidants β-carotene and tea polyphenols were used to assess their protective effects against γ-radiation induced sex-linked recessive lethal (SLRL) mutation and oxidative stress in Drosophila melanogaster. Third instar larvae and adult males of wild-type Oregon-K (ORK) were fed on test agents for 24 and 72 h respectively before exposure to 10Gy γ-irradiation. The treated/control flies were used to assess the induction of SLRLs. We also evaluated antioxidant properties of these phytochemicals in the third instar larvae.ResultsDifferent stages of spermatogenesis in adult males showed a decrease in γ-radiation induced SLRL frequencies upon co-treatment with test agents. A similar trend was observed in larvae. Furthermore, a significant increase in antioxidant enzymatic activities with a decrease in malondialdehyde content was observed.Conclusionβ-carotene and tea polyphenols have exerted antigenotoxic and antioxidant effects in Drosophila. This study demonstrated the suitability of Drosophila as an alternative to mammalian testing for evaluating the antigenotoxic and antioxidant activity of natural products.

Protective effects of tea polyphenols on exhaustive exercise-induced fatigue, inflammation and tissue damage

ABSTRACTBackground: The beneficial properties of tea polyphenols have been extensively studied; however, less attention has been paid to their effects, especially anti-inflammatory effect during exhaustive exercise.Objective: The present study assessed the potential protective effects of tea polyphenols against the fatigue, inflammation and tissue injury caused by an exhaustive exercise bout in rats.Design: Twenty-four healthy male rats were divided into three groups. Group C was a sedentary control group, Groups E+TP and Group E performed a single exhaustive swimming test; all groups had normal diets, but Group E+TP was supplemented with tea polyphenols. All rats were immediately euthanized after exhaustive exercise, and biochemical and inflammatory parameters, including lactic acid (LA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), lactic dehydrogenase (LDH), and creatine kinase (CK) activity levels, were measured. Reverse transcription (RT) and Real-Time PCR was employed to evaluate the mRNA expression of IL-1β in the liver.Results: The results showed a decrease in serum LA levels (22%, p < 0.05) in rats that consumed dietary tea polyphenols. Interestingly, dietary tea polyphenols decreased the serum levels of pro-inflammatory factors (TNF-α: 13%, p < 0.05; IL-1β: 10%, p < 0.05; and IL-6: 48%, p < 0.05) and shifted the serum IL-10/TNF-α ratio to a predominantly anti-inflammatory milieu (0.52 ± 0.07 vs. 0.67 ± 0.10, p < 0.01). Furthermore, the polyphenols effectively inhibited the release of tissue damage markers (CK: 24%, p < 0.05 and LDH: 28%, p < 0.05) in the serum and decreased IL-1β mRNA expression in the liver.Conclusions: This study indicated that tea polyphenols could significantly protect rats from the fatigue, inflammation and tissue damage induced by acute exhaustive exercise.

Tea polyphenols promote cardiac function and energy metabolism in ex vivo rat heart with ischemic/reperfusion injury and inhibit calcium inward current in cultured rat cardiac myocytes.

To investigate the protective effects of tea polyphenols (TP) against myocardial ischemia/reperfusion (IR) injuries and explore the possible mechanisms. Langendorff-perfused rat hearts were subjected to ischemia for 30 min followed by reperfusion for another 30 min. Myocardial function indices were measured by a left ventricular cannula via a pressure transducer connected to the polygraph in isolated Langendorff hearts and energy metabolism was measured using (31)P nuclear magnetic resonance (NMR) spectroscopy. Whole-cell atch-clamp technique was used to record calcium inward current (I(Ca-L)) in cultured rat cardiac myocytes. Compared with the control hearts, the ex vivo rat hearts with 2.5 mg/L TP treatment showed significantly increased left ventricular developed pressure (LVDP), maximal rise rate of LVDP (+dp/d(tmax)), maximal fall rate of LVDP (-dp/dt(max)), and coronary flow (CF) (P<0.05). During both cardiac ischemia and reperfusion phase, ATP and PCr levels were elevated significantly in TP-treated hearts compared with those in the control hearts (P<0.05). In cultured rat cardiac myocytes, ICa-L was remarkably decreased by TP at the doses of 2.5 and 5.0 mg/L (P<0.01). Our results support a possible protective role of TP against myocardial IR injury by improving myocardial energy metabolism and inhibiting I(Ca-L) in the cardiac myocytes.

Regulating Effect of Tea Polyphenols on Endothelin, Intracellular Calcium Concentration, and Mitochondrial Membrane Potential in Vascular Endothelial Cells Injured by Angiotensin II

Polyphenols are the main active component of tea and are considered an antiatherosclerosis agent, protecting vascular endothelial cells (VECs) from injury and preventing cardiovascular diseases. Endothelin level, intracellular calcium concentration, and mitochondrial membrane potential in VECs directly reflect the function and injury status of cells. The objective of this study was to study the regulating effects of tea polyphenols on these factors in VECs injured by angiotensin II (Ang-II) and explore the protective effect of tea polyphenols on human VECs. In this study, human aortic vascular endothelial cells were divided into 4 groups: (1) a control group; (2) Ang-II group: Ang-II at a concentration of 10(-7) mol/L was added to the cells; (3) low-concentration tea polyphenols + Ang-II group: tea polyphenols at a concentration of 5 mg/L was added in addition to Ang-II; (4) high-concentration tea polyphenols + Ang-II group: tea polyphenols at a concentration of 25 mg/L was added in addition to Ang-II. One hundred microliters of supernatant was extracted before treatment and at 0.5, 6, and 24 hours after treatment in each group to establish the content of endothelin. The results showed the following: (1) tea polyphenols decreased the expression of endothelin-1 messenger RNA, which was increased by Ang-II (P < 0.01). (2) Tea polyphenols inhibited endothelin secretion induced by Ang-II (P < 0.01), and the inhibition of low-concentration tea polyphenols was superior to that of high concentration tea polyphenols (P < 0.01). (3) Tea polyphenols ameliorated the changes in intracellular calcium concentration and mitochondrial membrane potential induced by Ang-II (P < 0.01). This study suggests that tea polyphenols may effectively protect VECs against injury by regulating endothelin, intracellular calcium concentration, and mitochondrial membrane potential in VECs injured by Ang-II. Additionally, lower dose would be used clinically rather than the higher dose for obtaining better results.

Protective effects of tea polyphenols against the destruction of melanocytes by CD8+ T ceils from vitiligo patients

Objective To evaluate the protective effects of tea polyphenols against the destruction of melanocytes by CD8+ T cells from vitiligo patients.Methods Skin tissue was resected from the margin of vitiligo lesions followed by the isolation and culture of CD8+ T lymphocytes,and from the normal skin of vitiligo patients followed by the isolation and culture of melanocytes.Flow cytometry was carried out to evaluate the purity of CD8+ T cells.The melanocytes were cocultured with the CD8 + T cells at different ratios followed by the evaluation of killing effect of CD8+ T cells.Various concentrations (200 and 400 μg/ml) of tea polyphenols were added into the co-culture system of CD8+ T cells and melanocytes at a ratio of 5 ∶ 1 followed by an additional culture of 48 hours.Then,flow cytometry was performed to detect the apoptosis in melanocytes in the coculture system.Results CD8+ T lymphocytes were successfully obtained from the marginal area of vitiligo lesions with a purity of more than 90％,which highly expressed the antigens CD137 and CD69.The coculture with CD8+ T cells markedly accelerated the apoptosis in melanocytes,while the accelerative effect was inhibited by tea polyphenols of 200 and 400 μg/ml.Conclusions The CD8+ T cells infiltrating the edge of vitiligo lesions display a potential destructive effect on autologous melanocytes from vitiligo patients,and tea polyphenols have a protective effect against the destruction of melanocytes by CD8+ T cells. Key words: Vitiligo; T-lymphocytes, cytotoxic; Melanocytes; Tea polyphenols

Protective effect of tea polyphenols on the blood-brain barrier

AbstractThis study was to investigate the protective effects of tea polyphenols on the blood-brain barrier (BBB) of rats with global cerebral ischemia/reperfusion (GCIR) injury. Sprague Dawley rats underwent four-vessel occlusion to construct the model of GCIR. Half an hour before complete occlusion, they were treated with tea polyphenols (TP) (6.4%; 100 or 200 mg/kg) via tail intravenous injection. 24 h after reperfusion, BBB permeability was evaluated by measuring brain water content (BWC) and residual amount of Evan’s blue dye in cerebral tissue. In addition to this, MMP-9 and collagen IV protein expression in cerebral tissue were also detected using immunohistochemistry. ANOVA and SNK-q were used to do statistical analysis. Statistical significance was considered at P&lt;0.05. Compared to the untreated, the TP-treated rats had significantly decreased BWC (P&lt;0.05), decreased residual amount of Evan’s blue dye in cerebral tissue (P&lt;0.05), down-regulated MMP-9 (P&lt;0.05) and up-regulated collagen IV expression in brain tissue (P&lt;0.05). It can be concluded from these findings that TP may reduce the MMP-9 mediated collagen IV degradation caused by GCIR to protect the BBB.

Excitotoxicity and oxidative damages induced by methylmercury in rat cerebral cortex and the protective effects of tea polyphenols

Methylmercury (MeHg) is a highly neurotoxic environmental pollutant that has a high appetency to the central nervous system. The underlying mechanisms of MeHg-induced neurotoxicity have not been elucidated clearly until now. Therefore, to explore the mechanisms contribute to MeHg-induced neurotoxicity, rats were exposed to different dosage of methylmercury chloride (CH3 ClHg) (0, 4, and 12 μmol kg(-1)) for 4 weeks to evaluate the neurotoxic effects of MeHg. In addition, considering the antioxidative properties of tea polyphenols (TP), 1 mmol kg(-1) TP was pretreated to observe the possible protective effects on MeHg-induced neurotoxicity. Then Hg, glutamate (Glu) and glutamine (Gln) levels, glutamine synthetase (GS), phosphate-activated glutaminase (PAG), Na(+)-K(+)-ATPase, and Ca(2+)-ATPase activities, intracellular Ca(2+) level were examined, glutathione (GSH), malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and reactive oxygen species (ROS) levels, N-methyl-D-aspartate receptors (NMDARs) mRNA and protein expressions, apoptosis level and morphological changes in the cerebral cortex were also investigated. Study results showed that compared with those in control, exposure to CH3 ClHg resulted in excitotoxicity in a concentration-dependent manner, which was shown by the Glu-Gln cycle disruption and intracellular Ca(2+) homeostasis disturbance. On the other hand, CH3 ClHg exposure resulted in oxidative damages of brain, which were supported by the significant changes on GSH, MDA, sulfhydryl, carbonyl, 8-OHdG, and ROS levels. Moreover, apoptosis rate increased obviously and many morphological changes were found after CH3 ClHg exposure. Furthermore, this research indicated that TP pretreatment significantly mitigated the toxic effects of MeHg. In conclusion, findings from this study indicated that exposure to MeHg could induce excitotoxicity and oxidative damage in cerebral cortex while TP might antagonize the MeHg-induced neurotoxicity.

The Protective Effects of Tea Polyphenols and Schisandrin B on Nephrotoxicity of Mercury

Mercury (Hg) is an occupational and environmental contaminant that is a well-recognized health hazard. To approach the concrete mechanisms of mercury nephrotoxicity and find out a new way to prevent it, the rats were subcutaneously injected with different dosages of mercuric chloride (HgCl(2))--0, 2.2, 4.4, and 8.8 μmol/kg. The levels of Hg, blood urea nitrogen (BUN), urine protein, glutathione (GSH), malondialdehyde (MDA) and activities of N-acetyl-beta-D-glucosaminidase (NAG), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were investigated, and the levels of reactive oxygen species (ROS) and apoptosis and the pathological changes were also observed. In addition, the effects of 1 mmol/kg tea polyphenols (TP) and 0.04 mmol/kg schisandrin B (Sch B) were studied at 8.8 μmol/kg HgCl(2). It was observed that the levels of Hg, BUN, urine protein, GSH, and MDA and activities of NAG, ALP, and LDH increased significantly; the activities of SOD and GSH-Px decreased significantly; the levels of ROS and apoptosis increased obviously; and many pathological changes occurred dose-dependently in the HgCl(2) injection groups. Further investigation indicated that pretreatment with TP and Sch B significantly reversed the toxic effects of HgCl(2). These results suggested that TP and Sch B might antagonize the nephrotoxicity caused by HgCl(2) exposure.

Tea polyphenols protect against irradiation-induced injury in submandibular glands’ cells: A preliminary study

To study the protective effect of tea polyphenols (TPs) on submandibular glands affected by radiation injury. Sixty rats were randomly divided into radiation group (R-group, N = 30) and TP-pre-treated-radiation group (TPR-group, N = 30). The rats were intragastrically administered with TP or normal sodium from 14 days before radiation, continuously daily, until the experiment. All the rats in both groups were irradiated with a single exposure dose of 15 Gy gamma rays that were delivered to the head and neck areas. Ten rats of each group were anatomised on the 3rd, 6th and 30th day after irradiation, respectively. The submandibular glands of the rats were removed for the study. The morphologic changes of the submandibular glands were observed by transmission electron microscopy (TEM). The terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick-end labelling (TUNEL) method was used to detect apoptosis of the submandibular glands' cells. Electron microscope observation of the submandibular glands showed that the lesions of the TPR-group were mild. Change in apoptosis of the cells was not obvious compared with the R-group. The cell apotosis was typical after irradiation in the R-group. Apoptosis index that was detected in the cells of submandibular glands of the TPR-group was statistically significantly decreased compared with the R-group (P < 0.01) on the 3rd, 6th and 30th day after irradiation. TP could protect submandibular glands from radiation injuries, and the protection mechanism may be realised by anti-apoptosis.

The protective effects of tea polyphenols on the function of organs

Tea is widely accepted as a beverage all over the world, and as the technology developed, various studies have clearly demonstrated tea polyphenols possess potent neuroprotective effect. This effect has been attributed to their potent antioxidan, free radical scavenging, anti -inflammatory, regulating signal pathway actions, ect.. This article reviews the protective effects of tea polyphenols on the function of organs from these aspects; provides theoretical basis for clinical use,fundamental research and development of tea polyphenols' new products. Key words: Tea polyphenols; Ischemia/reperfusion; Brain protection

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significanly correlated with cytochrome P450 suppression

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

Protective effects of tea polyphenols on liver against triptolide-induced hepatic injury in mice

Protective effects of tea polyphenols on liver against triptolide-induced hepatic injury in mice

Protective effects of tea polyphenols and caffeine

Compounds derived from botanical sources, such as polyphenols from tea, have been of interest as possible therapeutic agents. Their benefits in terms of cancer chemoprevention have also been investigated primarily through in vitro and animal in vivo studies. Ultraviolet light from solar radiation has been proven to initiate and promote skin cancer, which is the most common malignancy in light-skinned populations. This review discusses the effects of tea polyphenols in preventing cutaneous carcinogenesis. Although many of the mechanisms and pathways discussed may be applicable to other carcinogens, this review focuses mainly on those related to ultraviolet light-induced processes and potential action sites for tea polyphenols. Since caffeine is a component of tea, and has also been suggested as a possible chemoprotective agent, it is included in this review. Based on data from numerous studies published in the scientific literature, tea polyphenols are promising chemopreventive agents against ultraviolet-induced skin cancers. Their antioxidant properties, inhibitory effects on signal transduction pathways, cell proliferation, angiogenesis and capacity for apoptosis induction, as well as possible immune protective effects, are among the mechanisms that contribute to skin cancer prevention.

ULTRAVIOLET RADIATION AND REACTIVE OXYGEN GENERATION AS INDUCERS OF KERATINOCYTE APOPTOSIS: PROTECTIVE ROLE OF TEA POLYPHENOLS

Ultraviolet A (UVA) radiation produces serious damage to skin, especially to dermis, but its damage to epidermis and responsible mechanisms are not fully understood. Studies were thus undertaken to investigate the effects of UVA or reactive oxygen species (ROS) on lipid peroxidation, cell cycle, and apoptosis in primary cultured rat keratinocytes and to determine the possible protective effects of tea polyphenols (TPP). UVA or ROS increased the release of plasma enzyme lactate dehydrogenase (LDH), and increased lipid peroxidation production (malondialdehyde, MDA), but decreased the activity of glutathione peroxidase (GSH-Px), indicating that UVA or ROS were cytostatic and peroxidizing to keratinocytes. TPP stabilized and protected cell membranes from ROS or UVA by inhibiting the release of LDH, lowering MDA levels, and increasing GSH-Px activity. Flow cytometry (FCM) analysis revealed that UVA or ROS decreased the proliferative index (PI); hence the cell growth was blocked in the S/G2 phase, with an increase in the percentage of apoptosis in primary keratinocytes. TPP modified the UVA or ROS-induced changes in PI and apoptosis. TPP may be useful to protect keratinocytes from UVA irradiation. In summary, these data demonstrated that UVA damage to skin keratinocytes in vitro was similar to that for ROS and that TPP protects against UVA-induced cytotoxicity by inhibiting lipid peroxidation and apoptosis.

Inhibition of nitrous acid-dependent tyrosine nitration and DNA base deamination by flavonoids and other phenolic compounds.

Exposure of tyrosine or DNA bases to acidic nitrite at low pH results in the nitration of tyrosine and the formation of base deamination products, respectively. At pH 1, hypoxanthine and xanthine are formed from the deamination of adenine and guanine, respectively, whereas under the same conditions, uracil is not detected. The yield of 3-nitrotyrosine derived from interaction of equimolar nitrite and tyrosine at pH 1 is approximately 50% of that obtained from equimolar peroxynitrite-tyrosine interactions at pH 7. 4. The ability of a range of plant phenolic constituents to prevent damage mediated by acidic nitrite was also examined in comparison with the activity of vitamin C. The epicatechin/gallate family of flavonols, constituents of green tea, red wine, etc., demonstrates the most extensive inhibitory properties against both tyrosine nitration and base deamination. The results also show that ascorbic acid is a poor inhibitor of nitration or deamination under acidic conditions such as those of the stomach. The ability of plant phenolics to scavenge reactive nitrogen species derived from acidic nitrite may contribute to the protective effects of tea polyphenols against gastric cancer.