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Rutaecarpine And Maxell Wind Dan On The Liver And Kidney Of Transporters

Posted on:2015-01-30Degree:MasterType:Thesis
Country:ChinaCandidate:Q N ZhuFull Text:PDF
GTID:2264330422974754Subject:Pharmacology
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Objective: To examine the effects of rutaecarpine on the expression of drug processinggenes, including Phase-1(P450enzyme genes), glucuronidation and sulfation genes anddrug transporters in liver of mice.Methods: Mice were orally administered rutaecarpine at the doses of10,20, and30mg/kg for consecutive7days. Collected blood and liver. Subjected total RNA to real-timeRT-PCR analysis.Results: Rutaecarpine administration induced Cyp3a11and Cyp4a10. For phase-2enzyme genes, rutaecarpine increased glucuronyltransferases (Ugt1a1and Ugt1a6), buthad no effects on sulfotransferase (Sult1a1and Sult1b1). Most interestingly, rutaecarpineincreased hepatic uptake of organic anion transporting peptides (Oatp1a1, Oayp1a4,Oatp1b2, and Oatp2b1) and induced effl ux transporter such as multidrugresistance-associated proteins (Mrp1, Mrp2, Mrp3, and Mrp4), especially at the doses of20mg/kg and above.Conclusion: The interactions of rutaecarpine with drugs involve of hepatic transportersand phase-2enzyme genes. The effects of rutaecarpine on these drug processing genescould play integrated roles in producing herb–drug interactions. Objective: To study renal mercury (Hg) accumulation, the expression of kidney injurymolecule-1(Kim-1) and transporters following Wan-Sheng-Hua-Feng Dan (WSHFD) andmercuric chloride administration.Methods: SD rats were orally administered with WSHFD without cinnabar (HgS)(WSHFD0,1.5g·Kg-1), WSHFD contained3.5%cinnabar (WSHFD2,1.5g· kg-1), WSHFDcontained10%cinnabar (WSHFD3,1.5g·kg-1), and mercuric chloride (HgCl2,18mg·kg-1)for7days.Results: The Hg accumulation after HgCl2was45ng·mg-1, and the rest groups were1-2ng· mg-1; HgCl2group had25-fold higher Kim-1expression,2.3-fold lower Oat1expression, and3-fold higher Mate2k and Mrp4expression as compared to rest groups.There were no differences in gene expression among WSHFD0, WSHFD2, and WSHFD3under experimental conditions.Conclusion: WSHFD with10-fold higher Hg content is much less effective than HgCl2inproducing kidney Hg accumulation, Kim-1expression, and transporter expression. objective: To examine the regulation of bile acid synthesis and transport in normalpregnant and lactating rats.Materials and Methods: Livers from timed pregnant SD rats were collected ongestational days10,14and19, and postnatal days1,7,14and21. Determined Total bileacids and total RNA was isolated to real time RT-PCR analysis.Results: Hepatic bile acids were not elevated during pregnancy but increased duringlactation under physiological conditions. Bile acid synthesis rate-limiting enzyme Cyp7a1was unchanged in gestations days, but increased on PND14and21. Expression of Cyp8b1,Cyp27a1and Cyp7b1was also higher during lactation. Conclusion: Hepatic bile acidhomeostasis is maintained during normal pregnancy in rats. Together with increasedexpression of bile acid efflux transporter, the expression of bile acid synthesis genes andliver bile acid accumulation were increased during lactation,...
Keywords/Search Tags:Rutaecarpine, Herb–drug interaction, Cytochrome P450, Glucuronidation, Hepatic transportersWan-Sheng-Hua-Feng Dan (WSHFD), Mercuric chloride (HgCl2), Cinnabar(HgS), Renal Hg accumulation, Renal Kim-1and transporterPregnant and lactating rats
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