1. Background and Objectives:
MOLECULAR MECHANISMS BY WHICH WHITE TEA INTAKE PREVENTS OXIDATIVE-INDUCED STRESS IN VIVO
Authors: C. Espinosa1, F. Pérez-Llamas1, F. A. Guardiola2, M. A. Esteban2, M. B. Arnao3, S. Zamora1, J. A. López-Jiménez1
1Physiology Department.2Fish Innate Immune System Group, Department of Cell Biology and Histology. 3Department of Plant Biology (Plant Physiology), Faculty of Biology, Campus Regional de Excelencia Internacional “Campus Mare Nostrum”, University of Murcia, 30100, Spain
Background and Objectives:
Tea (Camellia sinensis) has beneficial properties in the prevention of diseases such as cancer, heart disease and neurodegenerative diseases. These properties, which have been attributed to the flavonoid content of tea, may be beneficial in pathological situations associated with a high production of free radicals. However, physiological mechanisms associated with the chemical properties of polyphenols and their antioxidant effects on health are still controversial. Protective genes, the products of which could reduce oxidative stress, contain a common promoter element called the antioxidant response element (ARE). Several transcription factors can bind the ARE, which is a cis-acting DNA regulatory element that activates the promoter region of many genes encoding phase II detoxification enzymes and antioxidants. The nuclear factor E2-related factor 2 (Nrf2) is responsible for activating transcription in response to oxidative stress. Green tea polyphenols are believed to initiate a cellular antioxidant response, which results in the induction of a variety of metabolic genes. The genes for each of these enzymes are known to contain functional electrophile/AREs (EpRE/AREs). In vivo, ADR is able to generate a large number and variety of free radicals with cytotoxic effects. Clinical studies in humans have shown that treatment with some antioxidants does not fully reverse the cardiotoxic effect of ADR, and research is ongoing to identify new agents to reverse this secondary effect. The objective of this study was to investigate mechanisms through which the ingestion of white tea extract protects against acute oxidative stress.
Methods:
To shed light on this issue, rats were given distilled water (controls), 0.15 mg/d (dose 1) or 0.45 mg/d (dose 2) of solid tea extract/kg body weight for 12 months. All the animals received an injection of adriamycin (ADR) (10 mg/kg body weight), except half of the control group, which were given an injection of saline solution. In the liver, the expression of the nuclear factor E2-related factor 2 (NRF2), NAD(P)H:quinone oxidoreductase (NQO1), glutathione–S–transferase (GST) and heme oxygenase1 (HO1) was analysed by real-time PCR, and the activity of catalase (Cat), superoxide dismutase (Sod) and glutathione reductase (Gr) was measured spectrophotometrically.
Results:
ADR significantly increased the expression of NRF2, GST NQO1 and HO1 with respect to the control rats and also increased the activity of CAT, SOD and GR. The intake of white tea increased the expression of NRF2, GST1, NQO1 and HO1 in the ADR group compared with the control group and decreased the activity of CAT, SOD and GR in a dose-dependent manner.
Conclusions:
We conclude that the long-term intake of white tea extract activates the Nrf2/ARE response associated with the detoxification of xenobiotics and the neutralisation of ADR before it can cause increased oxidative damage. These data explain the beneficial effects of tea extract in reducing oxidative damage and cytotoxicity caused by ADR. The antioxidant activity of white tea seems to play an important role in the regulation of the activity of the antioxidant enzymes CAT, SOD and GR. Our results reveal that the quantity and the quality of white tea polyphenols and catechins administered were sufficient to neutralise free radicals and the resulting oxidative stress. It was not necessary to increase the level of the corresponding enzymes, a fact confirmed and reinforced by the reduction becoming more evident in response to an increased dose of the tea extract.
Additional studies of effects of particular polyphenols on the expression of AREs and antioxidative enzymes can shed light on mechanisms responsible for the regulation of nutritional factors.
This work was supported by the ‘‘Ministerio de Ciencia y Tecnología” of Spain under project AGL C02-01 and Beca FPU (AP ).
Keywords:
Adryamicin; ARE response; Nrf2; Polyphenols; White tea
P0191