ABSTRACT
BACKGROUND: White tea infusion (Camelia sinensis) has antioxidants properties. The infusion contains polyphenols that have been proposed to induce antioxidant response element (ARE) response via nuclear factor E2-related factor 2 (NRF2). Adriamycin (ADR) has antitumour properties and oxidative effects. Oxidative stress is related to a variety of kidney diseases. Prevention of the oxidative stress through long-term intake of white tea and the study of the molecular mechanisms involved in protection could be of great interest. Rats were given distilled water, 0.015 or 0.045 g of solid white tea extract kg(-1) body weight for 12 months. Animals received an injection of ADR. In kidney, oxidative stress parameters were measured, the expressions of nuclear factor E2-related factor 2 gene (Nrf2), and detoxifying and antioxidants genes were analysed, and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) were measured. RESULTS: ADR administration increased oxidative parameters and decreased the antioxidant activity; significantly increased the expression of analysed genes and the activity of CAT and SOD and decreased GR activity. The highest white tea dose protected redox status and inhibited ARE response. CONCLUSION: Long-term intake of white tea protected kidney against the oxidative stress. ADR activated the ARE response but in animals treated with the highest dose of white tea, this response was inhibited, probably for antioxidant protection. © 2015 Society of Chemical Industry.
Subject(s)
Antibiotics, Antineoplastic/adverse effects , Antioxidants/therapeutic use , Doxorubicin/adverse effects , Kidney/drug effects , Oxidative Stress/drug effects , Renal Insufficiency/prevention & control , Tea , Animals , Antioxidant Response Elements , Antioxidants/administration & dosage , Antioxidants/isolation & purification , Camellia sinensis/chemistry , Camellia sinensis/growth & development , Female , Food Handling , Freeze Drying , Gene Expression Regulation , Kidney/metabolism , Kidney/physiopathology , Male , NF-E2-Related Factor 1/agonists , NF-E2-Related Factor 1/antagonists & inhibitors , NF-E2-Related Factor 1/genetics , NF-E2-Related Factor 1/metabolism , Oxidation-Reduction , Oxidoreductases/antagonists & inhibitors , Oxidoreductases/chemistry , Oxidoreductases/genetics , Oxidoreductases/metabolism , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Plant Leaves/growth & development , Plant Shoots/chemistry , Plant Shoots/growth & development , Rats, Sprague-Dawley , Renal Insufficiency/chemically induced , Renal Insufficiency/metabolism , Renal Insufficiency/physiopathology , Tea/chemistryABSTRACT
Nuclear factor erythroid-derived 2-related factor 1 (Nrf1) regulates cellular stress response genes, and has also been suggested to play a role in other cellular processes. We previously demonstrated that hepatocyte-specific deletion of Nrf1 in mice resulted in spontaneous apoptosis, inflammation, and development of liver tumors. Here, we showed that both fibroblasts derived from Nrf1 null mouse embryos and fibroblasts expressing a conditional Nrf1 allele showed increased micronuclei and formation of abnormal nuclei. Lentiviral shRNA-mediated knockdown of Nrf1 in SAOS-2 cells also resulted in increased micronuclei, abnormal mitosis and multi-nucleated cells. Metaphase analyses showed increased aneuploidy in Nrf1(-/-) embryonic fibroblasts. Nuclear defects in Nrf1-deficient cells were associated with decreased expression of various genes encoding kinetochore and mitotic checkpoint proteins. Our findings suggest that Nrf1 may play a role in maintaining genomic integrity, and that Nrf1 dysregulation may induce tumorigenesis.