Beverage–Drug Interaction: Effects of Green Tea Beverage Consumption on Atorvastatin Metabolism and Membrane Transporters in the Small Intestine and Liver of Rats

Abstract

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.

Subcellular distribution of ezrin/radixin/moesin and their roles in the cell surface localization and transport function of P-glycoprotein in human colon adenocarcinoma LS180 cells

“…Unlike LS180 cells, Caco-2 cells were deficient in moesin, which is in agreement with previous findings [45], implying a characteristic feature of LS180 cells, which carries genes for all three ERM proteins. Accumulating evidence indicates that P-gp is highly expressed not only in the cells derived from human gastrointestinal epithelium, including LS180 and Caco-2 cells [46][47][48], but also in the gastrointestinal tissues of rodents [49][50][51][52][53][54]. These previous findings strongly support the results obtained in the present study, indicating the gene expression pattern and subcellular localization of ERM along with P-gp in LS180 cells.…”

Evaluation of the effects of four types of tea on the activity of cytochrome P450 enzymes with a probe cocktail and HPLC–MS/MS

“…Due to interspecies differences, in vitro studies have suggested variation in the degree to which tea extracts (mainly green tea) inhibit the activity of CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2D6, and CYP3A4 ( 43 , 44 ). Rat models have shown reduced enzyme activity of CYP2C, CYP2E1, and CYP3A with green and black tea treatment ( 45 , 46 ), as well as increased CYP3A activity with oolong tea ingestion ( 47 ). Given the regional differences and slight changes in tea processing techniques, the results obtained in this study may differ from those of previous studies.…”

Herb–Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplements

“…They found intestinal CYP3A4 activity to be lowered, and hepatic CYP3A4 activity increased. OATP2 expression was decreased, which could have led to limited hepatic uptake [ 204 ].…”