Biliary clearance of bromosulfophthalein in anesthetized and freely moving conscious rat

Oh, Ju‐Hee; Park, Se-Eun; Shim, Chang‐Koo; Lee, Young‐Joo

doi:10.1002/bdd.646

Cited by 6 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggested that the decreases in Oatp1a1 and Oatp2b1 expression levels at 1 h after intestinal I/R might cause the suppression of liver uptake of BSP, resulting in the high AUC0-90, the low CLtot and CLbile (Table 3). The CLtot and CLbile values in this study are almost consistent with the previous report in other group (28). Moreover, the difference of CLtot between intestinal I/R rats reperfused for 1 h and sham-operated rats was almost same as the difference of CLbile ( Table 3), suggesting that the low CLtot value of BSP in intestinal I/R rats reperfused for 1 h was caused by the suppression of biliary excretion.…”

Section: Discussionsupporting

confidence: 91%

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Maruyama¹,

Ogura²,

Fujikawa³

et al. 2013

J Pharm Pharm Sci

View full text Add to dashboard Cite

-Purpose. Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. Methods. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Results. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC0-90) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CLtot) and the biliary clearance (CLbile) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Conclusions. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

show abstract

Section: Discussionsupporting

confidence: 91%

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Maruyama¹,

Ogura²,

Fujikawa³

et al. 2013

J Pharm Pharm Sci

View full text Add to dashboard Cite

show abstract

“…20,21) Pharmacokinetics of Curcumin in EHBR The jugular vein (for drug administration), carotid artery (for blood sampling), and bile duct of each rat were cannulated with polyethylene tubing (Natsume, Tokyo, Japan) under anesthesia at doses of 25 mg/kg and 25 mg/kg for tiletamine and zolazepam, respectively. 22,23) Cannulae were filled with heparinized saline (20 IU/mL) to prevent blood clotting.…”

mentioning

confidence: 99%

Biliary Excretion of Curcumin Is Mediated by Multidrug Resistance-Associated Protein 2

Lee

2012

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Curcumin has a wide spectrum of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Recently, its potential as effective chemoprevention against cholangiocarcinoma, a highly malignant tumor of the bile duct with limited therapeutic options, was reported. The purpose of the present study was to investigate the contribution of multidrug resistance-associated protein 2 (Mrp2) to the biliary excretion of curcumin using Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic rats (EHBR). After intravenous administration of curcumin with a loading dose of 4.5 mg/kg, followed by a constant infusion of 18 mg/kg/h to the SDR and EHBR, the pharmacokinetic parameters of curcumin were estimated. In EHBR, the total area under the bile concentration-time curve from 0 to 80 min following curcumin administration was dramatically decreased (0.094%) compared to that in SDR. In addition, the plasma-to-bile and liver-to-bile clearances were both significantly decreased compared to SDR. These results provide the first evidence that Mrp2 mediates the biliary excretion of curcumin and thus may be a major factor in the control of exposure of curcumin to the bile duct. This study may be helpful to the potential use of curcumin as a treatment for bile duct cancer, and to understanding the genetic polymorphism of Mrp2 for clinical trials of curcumin.

show abstract

“…Male SpragueDawley rats (8-9 weeks old, weighing 280-325 g) were obtained from Orient Bio (Seoul, South Korea). The procedures used for housing and maintenance of rats were similar to a reported method (Oh et al, 2009 …”

Section: Ratsmentioning

confidence: 99%

“…The procedures used for the cannulation of the jugular vein and/or the right femoral veins were similar to a reported method (Oh et al, 2009). The rats were anesthetized with intraperitoneal ketamine (33.3 mg kg ).…”

Section: Intravenous and Oral Studiesmentioning

confidence: 99%

Dose‐dependent pharmacokinetics of toxic metabolites is not related to increased toxicity following high‐dose valproic acid in rats

Jung

Kim

Lee

et al. 2010

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

It has been reported that urinary excretion of two metabolites of valproic acid (VPA), 4-ene-valproic acid (4-VPA)and 2,4-diene-valproic acid (2,4-VPA), increased exponentially with the administration of high doses of VPA, and this increased formation of toxic metabolites could be related to VPA hepatotoxicity in humans. The aim of this study was to investigate whether the plasma level of 4-VPA and 2,4-VPA in rats corresponds to the urinary data for the same metabolites in humans.After the oral administration of VPA at doses of 20, 100 and 500 mg kg-1 in rats, the AUC0–24 h, 4-VPA/AUC0–24 h, VPA ratios (0.0399,0.0120 and 0.0100 for 20, 100 and 500 mg kg-1, respectively) and AUC0–24 h, 2,4-VPA/AUC0–24 h, VPA ratios (0.00104, 0.00201 and 0.00141, respectively) did not increase with increasing doses of VPA in rats. Thus, the plasma exposure of toxic metabolites normalized by dose remained unchanged (for 2,4-VPA) or even decreased (for 4-VPA) following high-dose VPA administration;this contradicts the findings of previous studies. Our results suggest that toxicity induced by high doses of VPA cannot be explained by a nonlinear increase of toxic metabolites in rats.

show abstract

Biliary clearance of bromosulfophthalein in anesthetized and freely moving conscious rat

Cited by 6 publications

References 30 publications

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Intestinal Ischemia-Reperfusion Suppresses Biliary Excretion of Hepatic Organic Anion Transporting Polypeptides Substrate

Biliary Excretion of Curcumin Is Mediated by Multidrug Resistance-Associated Protein 2

Dose‐dependent pharmacokinetics of toxic metabolites is not related to increased toxicity following high‐dose valproic acid in rats

Contact Info

Product

Resources

About