EXPERIMENTS ON RATS – EFFECTS ON DRUG-METABOLIZING ENZYMES:
Long-term ingestion of green tea increases UDP-glucuronosyl transferase activity in rats, and after being absorbed, catechins are metabolized by drug-metabolizing enzymes in various organs. Thus, the glucuronidation through UDP-glucuronosyl increased transferase induction is postulated to contribute to the anticarcinogenic effect of green tea by facilitating the metabolism of chemical carcinogens into inactive products that are readily excreted. The interaction between 2-amino-3-methylimidazol (4,5-f) quinoline (IQ) and green tea catechin metabolism was examined.
IQ is a pre-carcinogen that was originally detected in an extract of fried meat. The major route of IQ biotransformation in rats is cytochrome P450 in the first step, followed by conjugation to a sulfate and a glucuronide conjugate.
Green tea modifies IQ metabolism in rats, increasing the formation of IQ glucuronides, which are then excreted in the urine. Moreover, protection against cancers induced by polycyclic aromatic hydrocarbons by green tea catechins may be due to the inhibition of their cytochrome P450 metabolism, but the effect of green tea on cytochrome P450 enzymes depends on the particular form. The long-term consumption of green tea increases cytochrome P450 1A1 and 1A2 activities, but not 2B1 and 2E1 activities, in normal rats. However, it is difficult to draw conclusions about a beneficial effect of green tea against carcinogens involving only modulation of this metabolic pathway.
EFFECTS ON ANTIOXIDANT MARKERS AND OXIDATIVE STRESS
Green tea is a popular neutraceutical as an antioxidant.
Antioxidants are compounds that protect cells against the damaging effects of reactive oxygen species, such as singlet oxygen, superoxide, peroxyl radicals, hydroxyl radicals, and peroxynitrite. An imbalance between antioxidants and reactive oxygen species results in oxidative stress, leading to cellular damage.
Catechins are hypothesized to help protect against these diseases by contributing, along with antioxidant vitamins (i.e., vitamins C and E) and enzymes (i.e., superoxide dismutase and catalase), to the total antioxidant defense system.
In-vivo studies showed that green tea catechins increase total plasma antioxidant activity. Intake of green tea extracts also increases the activity of superoxide dismutase in serum and the expression of catalase in the aorta; these enzymes are implicated in cellular protection against reactive oxygen species. This action is combined with direct action on oxygen species by a decrease in the nitric oxide plasma species concentration.
Malondialdehyde, a marker of oxidative stress, also decreases after green tea intake. These results suggest that catechins could have a direct (antioxidant) or indirect (increase of activity or expression) effect.
Since catechins can act as antioxidants in vitro, they might prevent the oxidation of other antioxidants, such as vitamin E. However, ingestion of green tea catechins does not modify the plasma status of vitamins E and C in vivo. Nevertheless, one study reported that catechins increase vitamin E concentration in low-density lipoprotein and in this way could protect low-density lipoprotein against peroxidation.
Pilipenko et al. assessed the tolerance of tableted green tea and its effect on the antioxidant status indices. Twenty-five patients with different gastrointestinal pathologies were: included in the study and divided into treatment and control groups. The tolerance of tableted green tea was good in the treatment group, who showed better dynamics of quality-of-life indices, especially in scales of body pain and social functioning. There were no significant differences in biochemical analysis between the groups, which may indicate the safety of this product. Analysis revealed that the treatment group showed a decreased level of all antioxidant status indices, as reflected in a significant decreasing of the lipid peroxidation index from 4.63 to 4.14.
EFFECTS ON CARBOHYDRATE METABOLISM
Type II diabetes is a heterogeneous disorder that involves resistance of glucose and lipid metabolism in peripheral tissues to the biological activity of insulin and inadequate insulin secretion by pancreatic ß cells. Animal models of diabetes are available: Zucker rats, which are genetically obese; injection of streptozotocin or alloxan, which destroys pancreatic B cells; and treatment with sucrose- rich diets, which induces obesity and insulin resistance.
In a study by Sabu et al, administration of GTPS (500mg/kg) to normal rats increased glucose tolerance significantly at 60 minutes. GTPs were also found to reduce significantly serum glucose levels in alloxan diabetic rats at a dose of 100mg/kg. Continued daily administration (15 days) of the extract at 50 or 100mg/kg produced 29% and 44% reduction, respectively in the elevated serum glucose level produced by alloxan administration.
Elevated hepatic and renal enzymes produced by alloxan were found to be reduced significantly by GTPs. The serum lipid peroxidation level was increased by alloxan and reduced significantly by the administration of 100mg/kg of GTPs. Decreased liver glycogen resulting from alloxan administration showed a significant increase after GTP treatment. The GTP-treated group showed increased antioxidant potential, as seen from improvements in superoxide dismutase and glutathione levels.
However, catalase, lipid peroxidation, and glutathione peroxidase levels were unchanged. These results indicate that alterations in the glucose utilizing system and oxidation status in rats that were increased by alloxan were partially reversed by the administration of GTPs.
Catechins also reduced plasma triglyceride levels in an oral glucose-tolerance test in normal rats: Green tea extract intake reduced these values in both Zucker rats and rats fed a sucrose-rich diet. Several human- and animal based studies suggested that green tea and its flavonoids have antidiabetic effect. Green tea flavonoids were also shown to have insulin-like activities as well as insulin-enhancing activity.
The antihyperglycemic effect of black tea was reported by Gomeset al. EGCG was found to inhibit intestinal glucose uptake by the sodium-dependent glucose transporter SGLT1, indicating its increase in controlling blood sugar. Streptozotocin diabetic rats showed increased sensitivity to platelet aggregation and thrombosis, and this abnormality could be improved by dietary catechins from green tea. Alloxan produces oxygen radicals in the body, which cause pancreatic injury and are responsible for increased blood sugar.
Under in-vivo conditions, glutathione acts as an antioxidant, and its decrease was reported in a diabetes mellitus model. The increased glutathione content in the liver of the rats treated with GTPs may be one of the factors responsible for the inhibition of lipid peroxidation. Superoxide dismutase and catalase are the two major scavenging enzymes that remove the toxic free radicals in vivo. Vucicet al. reported that the activity of superoxide dismutase is low in diabetes mellitus.
The Mediterranean Islands (MEDIS) epidemiological study is a cross-sectional health and nutrition survey that aims to evaluate the association between various sociodemographic, bioclinical, dietary, and other lifestyle habits and the prevalence of the common cardiovascular disease risk factors (i.e.. hypertension. dyslipidemia, diabetes, and obesity) among elderly people without a history of any chronic disease and living in the Mediterranean islands. Because data relating tea consumption with clinical characteristics are lacking in elderly populations, in the context of the MEDIS study, the authors sought to evaluate whether green tea consumption is independently associated with fasting blood glucose levels and the prevalence of type II diabetes mellitus. An earlier study was aimed at providing evidence of improvement in glucose metabolism in diabetic mice and healthy humans upon green tea consumption. Green tea promoted glucose metabolism in healthy human volunteers at 1.5 g/kgas shown in oral glucose-tolerance tests. Green tea also lowered blood glucose levels in diabetic db+/ db+ mice and streptozotocin-diabetic mice two to six hours after administration at 300mg/kg without affecting serum insulin level, whereas no effect was observed in control mice (+m/+m and normal ddY mice)
