ABSTRACT
Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).
Subject(s)
Animals , Male , Rats , Administration, Intravenous , Administration, Oral , Antihypertensive Agents , Blood , Pharmacokinetics , Apigenin , Blood , Pharmacokinetics , Bile , Metabolism , Chromatography, High Pressure Liquid , Drug Interactions , Erigeron , Chemistry , Glucuronates , Blood , Pharmacokinetics , Metabolic Clearance Rate , Multidrug Resistance-Associated Proteins , Metabolism , Plants, Medicinal , Chemistry , Random Allocation , Rats, Sprague-Dawley , Valsartan , Blood , PharmacokineticsABSTRACT
Objective To approach the effect of fluoride on the expression of thyroid peroxidase(TPO)activity and TPO mRNA in primary porcine thyrocytes.Methods Purified cultured porcine thyrocytes waft made into sodium fluoride model,and were divided according to the final concentration of NaF into 0(control group),40,80,160 mg/L.After exposed to NaF for 48 h,the morphology of the porcine thyrocytes was investigated with acridine orange staining method,TPO activity was measured with upgrade guaiacol method and RT-PCR method was used to detect the ratio of TPO/β-actin.Results The major changes included apoptotic bodies and cell fragments in the 80,160 mg/L groups under phase contrast microscope.With the increasing dose of fluoride.TPO activity,being(3.103±0.090),(1.944±0.025),(1.361±0.008),(0.668±0.026)U/L,respectively,had obviously lowered with a statistical significance compared between the groups(F=1563.864,P＜0.05).The TPO activity had a negative correlation with the dose of fluoride(r=-0.955,P＜0.05).With the dose of fluoride increasing,the expression of TPO mRNA had obviously lowered,being(0.947±0.013),(0.634±0.018),(0.448±0.028)and (0.210±0.009)with a statistical significance in group comparison(F=2713.855,P＜0.05).Conclusion Fluoride affects the thyroid via inhibiting TPO activity and expression of TPO mRNA.