研究指出茶中含有許多的兒茶素,且具有抗氧化和抗癌等益處。本研究將探討長期飲用市售含糖茶飲料對肝臟及肺臟藥物代謝酵素及氧化壓力之影響並探討含糖茶飲料與atorvastatin (ATV;Lipitor) 是否會產生交互作用,進行以下兩個實驗。實驗一:利用 HPLC/UV 進行市售茶飲料之成分分析與鑑定,並探討大鼠飲用市售含糖茶飲料五週後對其肝臟和肺臟藥物代謝酵素及氧化壓力之影響,將大鼠分成控制組 (去離子水)、市售綠茶組和紅茶組。實驗結果顯示,茶飲料顯著降低肝臟 CYP3A、2C 及 2E1之酵素活性,但會增加 CYP1A1 及 1A2 酵素活性;在 phase ІІ 酵素活性方面,肝臟及肺臟皆顯著增加 UDP-glucurosyltransferases (UGT) 活性;在氧化壓力方面,皆顯著性地增加肝臟和肺臟中 GSH 含量以及GSH/GSSG 之 ratio,然而,只有綠茶組會顯著增加肝臟中 GPx 及 GRx之酵素活性。實驗二:探討大鼠飲用市售含糖綠茶及紅茶飲料三週後對ATV 在血漿及肝臟中濃度之影響,並測定小腸和肝臟中運輸 ATV 的uptake 和 excretion 蛋白質表現,將大鼠分成控制組 (去離子水)、市售綠茶組和市售紅茶組實驗為期三週。結果在小腸方面紅茶組顯著抑制 CYP3A 酵素之活性;在肝臟方面,綠茶組顯著增加 CYP3A 酵素活性,紅茶組則顯著增加 UGT 活性,且無論綠茶或紅茶組皆顯著抑制肝臟uptake 運輸蛋白 Organic anion transporting polypeptides 2 (OATP2) 和excretion 運輸蛋白 Muti-drug resistance-associated protein 2 (MRP2)、MRP3 及 P-glycoprotein (P-gp) 蛋白表現量。綠茶組給予口服 ATV 後血漿中2-OH ATV 之藥物濃度曲線下面積 (AUC0-6hr) 高於控制組 (P<0.05),但ATV (AUC0-6hr)/2-OH ATV (AUC0-6hr) 比值則略低於控制組 (P<0.1),紅茶組則與控制組相比沒有差異;肝臟方面,綠茶組則顯著增加肝臟中 4-OH ATV 濃度。由以上結果顯示,長期飲用含糖茶飲料會增加肝臟和肺臟中的抗氧化能力並且調節藥物代謝系統,而當長期飲用茶飲料後再給予口服藥物 ATV 則可能會影響 ATV 在血漿及肝臟中的含量,而綠茶的作用比紅茶明顯可能與其含有較多之兒茶素有關。
Tea contains a lot of catechines and have beneficial effects on the prevention of many diseases. To investigate whether commercial tea drinks can cause drug interactions and their effects on drug-metabolizing systems and oxidatives stress in liver and lung, two experiments were conducted. Experiment І : HPLC/MS system was used to identify the components in tea drinks. Male Sprague-Dawley rats were fed a laboratory chow diet with de-ionized water (Control group) or green tea drink or black tea drink for 5 weeks. A significant increase in cytochrome P450 (CYP) 1A1-catalyzed ethoxyresorufin O-deethylation, CYP1A2-catalyzed methoxyresorufin O-demethylation and UDP-glucurosyltransferase in liver microsomes was observed in rats fed the diet with tea administration. However, CYP enzymes toward diclofenac 4-hydroxylation (CYP2C9), nitrophenol 6-hydroxylation (CYP 2E1) and testosterone 6β-hydroxylation (CYP3A) were significantly reduced by tea drinks administration. Furthermore, administered green tea drink or black tea drink to rats increased hepatic reduced glutathione/oxidized glutathione (GSH/GSSG) ratio but only those animals treated with green tea drink increased the activities of GSH peroxidase and GSH reductase. Our results suggest that green tea drink and black tea drink can modulate several CYP activities and oxidative stress in liver. Experiment ІІ : To investigate the effect of green tea and black tea drinks on drug-metabolizing systems and their effect on plasma and liver atorvastatin (ATV) and its major metabolite (2-OH ATV) concentrations in rats, male Sprague-Dawley rats were fed a chow diet with de-ionized water (Control group) or green tea drink or black tea drink for 3 weeks. A significant decrease in cytochrome P450 (CYP) 3A-catalyzed testosterone 6β-hydroxylation in intestine microsomes was observed in rats fed the diet with black tea drink administration. However, a significant increase in cytochrome P450 (CYP) 3A-catalyzed midazolam 1-hydroxylation in liver microsomes was observed in rats fed the diet with green tea drink administration. In addition, a significant increase in UDP-glucurosyltransferase (UGT) in liver microsomes was observed in rats fed the diet with black tea drink administration. Rats administrated with green tea drink and black teadrink significantly inhibited hepatic uptake transport proteins Organic anion transporting polypeptides 2 (OATP2) and excretion transport protein Muti-drug resistance-associated protein, 3 (MRP3) and P-glycoprotein (P-gp) expression. However, increased MRP2 protein expression was observed in both tea drinks treatment. In addition, plasma concentration of 2-OH ATV (AUC0-6h) was significantly increased in the green tea drink group compared with the control group. Moreover, green tea drink administration also tended to have higher plasma atorvastatin concentration (AUC0-6h) in rats. Rats administrated with green tea drink significantly increased 4-OH ATV concentration in the liver. These results suggest that long-term administration of commercially tea drinks may modulate drug-metabolizing systems and affect ATV metabolism and disposition. Moreover, tea drinks administration may also increase the antioxidant activities in the liver and lung.