RESUMO
Green tea (GT) beverages are popular worldwide and may prevent the development of many chronic diseases including cardiovascular disease and cancer. To investigate whether the consumption of a GT beverage causes drug interactions, the effects of GT beverage consumption on atorvastatin metabolism and membrane transporters were evaluated. Male rats were fed a chow diet with tap water or the GT beverage for 3 weeks. Then, the rats were given a single oral dose (10 mg/kg body weight (BW)) of atorvastatin (ATV), and blood was collected at various time points within 6 h. The results show that GT consumption increased the plasma concentrations (AUC0-6h) of ATV (+85%) and 2-OH ATV (+93.3%). GT also increased the 2-OH ATV (+40.9%) and 4-OH ATV (+131.6%) contents in the liver. Decreased cytochrome P450 (CYP) 3A enzyme activity, with no change in P-glycoprotein expression in the intestine, was observed in rats treated with GT. Additionally, GT increased hepatic CYP3A-mediated ATV metabolism and decreased organic anion transporting polypeptides (OATP) 2 membrane protein expression. There was no significant difference in the membrane protein expression of OATP2B1 and P-glycoprotein in the intestine and liver after the GT treatment. The results show that GT consumption may lower hepatic OATP2 and, thus, limit hepatic drug uptake and increase plasma exposure to ATV and 2-OH ATV.
RESUMO
The effect of commercially available green tea (GT) and black tea (BT) drinks on drug metabolizing enzymes (DME) and oxidative stress in rats was investigated. Male Wistar rats were fed a laboratory chow diet and GT or BT drink for 5 weeks. Control rats received de-ionized water instead of the tea drinks. Rats received the GT and BT drinks treatment for 5 weeks showed a significant increase in hepatic microsomal cytochrome P450 (CYP) 1A1 and CYP1A2, and a significant decrease in CYP2C, CYP2E1 and CYP3A enzyme activities. Results of immunoblot analyses of enzyme protein contents showed the same trend with enzyme activity. Significant increase in UDP-glucuronosyltransferase activity and reduced glutathione content in liver and lungs were observed in rats treated with both tea drinks. A lower lipid peroxide level in lungs was observed in rats treated with GT drink. Electrophoretic mobility shift assay revealed that both tea drinks decreased pregnane X receptor binding to DNA and increased nuclear factor-erythroid 2 p45-related factor 2 binding to DNA. These results suggest that feeding of both tea drinks to rats modulated DME activities and reduced oxidative stress in liver and lungs. GT drink is more effective on reducing oxidative stress than BT drink.
Assuntos
Camellia sinensis/química , Estresse Oxidativo , Chá/química , Animais , Antioxidantes/farmacologia , Cafeína/sangue , Colesterol/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromos/genética , Citocromos/metabolismo , Glutationa/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Subunidade p45 do Fator de Transcrição NF-E2/genética , Subunidade p45 do Fator de Transcrição NF-E2/metabolismo , Receptor de Pregnano X , Ratos , Ratos Wistar , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Triglicerídeos/metabolismoRESUMO
Applications of composite scaffolds comprising polyethylene oxide (PEO) and chitosan to the culture of bovine knee chondrocytes (BKC) were investigated. Here, PEO and chitosan with various weight ratios were crosslinked, refrigerated at -80 degrees C, and lyophilized. Pore surfaces of the PEO/chitosan scaffolds were chemically modified by human fibronectin for accelerating BKC adhesion and growth. The results revealed that the range of pore diameters was between 200 and 400 mum. A high content of PEO in scaffolds generated high porosity, moisture content, physical ductility, biodegradation rate, and BKC viability, as well as low Young's and compression moduli. High levels of PEO, human fibronectin, and extracellular calcium were favorable to the BKC culture, as indicated by the enhanced amounts of BKC, glycosaminoglycans, and collagen. However, a high concentration of medium potassium caused detrimental influences on the proliferation of BKC and the secretion of extracellular matrices. The present PEO/chitosan scaffolds showed enhancements in biomedical characteristics for the formation of tissue-engineered cartilage toward clinical prosthesis.