ABSTRACT
BACKGROUND: Growing attention has been paid to the effects of food flavor components on alleviating negative brain functions caused by stressful lifestyles. In this study, we investigated the alleviating effect of two kinds of black tea aromas on physical and psychological stress induced by the Uchida-Kraepelin test, based on salivary chromogranin-A (CgA) levels as a stress marker and subjective evaluations (Profile of Mood States). RESULTS: Compared with the water exposure control, inhaling black tea aroma (Darjeeling and Assam in this study) induced lower salivary CgA concentration levels after 30 min of mental stress load tasks. This anti-stress effect of black tea aroma did not differ between the two tea types even though the concentration of the anti-stress components in the Darjeeling tea aroma was higher than that in the Assam aroma. However, Darjeeling tea aroma tended to decrease the tension and/or anxiety score immediately after the first exposure. CONCLUSIONS: Inhaling black tea aroma may diminish stress levels caused by arithmetic mental stress tasks, and Darjeeling tea aroma tended to improve mood before mental stress load.
Subject(s)
Affect/drug effects , Chromogranin A/analysis , Odorants/analysis , Saliva/chemistry , Stress, Psychological/metabolism , Tea , Adult , Anxiety/metabolism , Female , Humans , Male , Task Performance and Analysis , Visual Analog Scale , Young AdultABSTRACT
The present study aims to investigate the role of P glycoprotein and multidrug resistance-associated protein (Mrp2) in the transport of telithromycin, a newly developed ketolide antibiotic, in vitro and in vivo. The in vitro experiments revealed that the intracellular accumulation of telithromycin in adriamycin-resistant human chronic myelogenous leukemia cells (K562/ADR) overexpressing P glycoprotein was significantly lower than that in human chronic myelogenous leukemia cells (K562/S) not expressing P glycoprotein. Cyclosporine significantly increased the intracellular accumulation of telithromycin in K562/ADR cells. When telithromycin was coadministered intravenously with cyclosporine in Sprague-Dawley (SD) rats, cyclosporine significantly delayed the disappearance of telithromycin from plasma and decreased its systemic clearance to 60% of the corresponding control values. Hepatobiliary excretion experiments revealed that cyclosporine almost completely inhibited the biliary clearance of telithromycin, suggesting that telithromycin is a substrate of P glycoprotein and a potential substrate of Mrp2. Moreover, the biliary clearance of telithromycin was significantly decreased by 80% in Eisai hyperbilirubinemic mutant rats with a hereditary deficiency in Mrp2, indicating that Mrp2, as well as P glycoprotein, plays an important role in the biliary excretion of telithromycin. When the effect of telithromycin on the biliary excretion of doxorubicin, a substrate of P glycoprotein and Mrp2, was examined in SD rats, telithromycin significantly decreased the biliary clearance of doxorubicin by 80%. Results obtained from this study indicate that telithromycin is a substrate of both P glycoprotein and Mrp2, and these transporters are involved in the hepatobiliary transport of telithromycin.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP-Binding Cassette Transporters/metabolism , Anti-Bacterial Agents/pharmacokinetics , Ketolides/pharmacokinetics , Liver/metabolism , Animals , Antibiotics, Antineoplastic/metabolism , Biological Transport/physiology , Cell Line, Tumor , Doxorubicin/antagonists & inhibitors , Doxorubicin/pharmacokinetics , Drug Resistance, Multiple , Liver/drug effects , Membrane Transport Proteins , Rats , Rats, Sprague-DawleyABSTRACT
P glycoprotein and multidrug resistance-associated protein 2 (Mrp2), ATP-dependent membrane transporters, exist in a variety of normal tissues and play important roles in the disposition of various drugs. The present study seeks to clarify the contribution of P glycoprotein and/or Mrp2 to the disposition of azithromycin in rats. The disappearance of azithromycin from plasma after intravenous administration was significantly delayed in rats treated with intravenous injection of cyclosporine, a P-glycoprotein inhibitor, but was normal in rats pretreated with intraperitoneal injection erythromycin, a CYP3A4 inhibitor. When rats received an infusion of azithromycin, cyclosporine and probenecid, a validated Mrp2 inhibitor, significantly decreased the steady-state biliary clearance of azithromycin to 5 and 40% of the corresponding control values, respectively. However, both inhibitors did not alter the renal clearance of azithromycin, suggesting the lack of renal tubular secretion of azithromycin. Tissue distribution experiments showed that azithromycin is distributed largely into the liver, kidney, and lung, whereas both inhibitors did not alter the tissue-to-plasma concentration ratio of azithromycin. Significant reduction in the biliary excretion of azithromycin was observed in Eisai hyperbilirubinemic rats, which have a hereditary deficiency in Mrp2. An in situ closed-loop experiment showed that azithromycin was excreted from the blood into the gut lumen, and the intestinal clearance of azithromycin was significantly decreased by the presence of cyclosporine in the loop. These results suggest that azithromycin is a substrate for both P glycoprotein and Mrp2 and that the biliary and intestinal excretion of azithromycin is mediated via these two drug transporters.
