We have previously demonstrated that moderate hyperbilirubinemia decreases blood pressure in ANG II-dependent hypertension through mechanisms that decrease oxidative stress and increase nitric oxide levels. Since decreases in renal hemodynamics play an important role in mediating the hypertensive actions of ANG II, the goal of the present study was to examine the effect of moderate hyperbilirub...

HSR-903 is a newly synthesized quinolone antibacterial agent with low toxicity. The biliary and urinary excretion of unchanged HSR-903, its R-isomer, and their glucuronides was determined after iv bolus administration (5 mg/kg) to normal Sprague-Dawley rats (SDR) and Eisai hyperbilirubinemic mutant rats (EHBR). The values for the biliary excretion clearance of HSR-903 and its glucuronide in EHB...

Although Oatp1a1 (rat organic anion-transporting polypeptide 1a1) was the transporter found responsible for the hepatocellular entry of enalapril (EN) into the rat liver, the canalicular transporter involved for excretion of EN and the metabolite, enalaprilat (ENA), was unknown. The Eisai hyperbilirubinemic rat (EHBR) that lacks Mrp2 (multidrug resistance-associated protein 2) was used to appra...

We developed a pravastatin derivative, sodium (3R,5R)-3,5dihydroxy-7-((1S,2S,6S,8S)-6-hydroxy-2-methyl-8-((1-[C]-(E)2-methyl-but-2-enoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1yl)heptanoate ([C]DPV), as a positron emission tomography (PET) probe for noninvasive measurement of hepatobiliary transport, and conducted pharmacokinetic analysis in rats as a feasibility study for future clinical study...

OBJECTIVE A recent study reported association of high bilirubin concentrations with decrease in basal vesical tonicity and relaxation of pre-contracted ureteral and vesical smooth muscles in vitro, and authors discussed that recovery of antenatal hydronephrosis might partly be associated with decreased bladder resistance to the urine flow due to hyperbilirubinemia. We aimed to investigate wheth...

Mdr1a-, Bcrp-, and Mrp2-knockout rats are a more practical species for absorption, distribution, metabolism, and excretion (ADME) studies than murine models and previously demonstrated expected alterations in the pharmacokinetics of various probe substrates. At present, gene expression and pathology changes were systematically studied in the small intestine, liver, kidney, and brain tissue from...

introduction: neonatal hyperbilirubinemia is a common disorder and if untreated is potentially neurotoxic. methods: in order to investigate the correlation between hyperbilirubinemia and hemoglobinopathies, in a prospective study we studied a total 100 full term neonates at nemazi hospital with total bilirubin greater than 15 mg/dl and direct bilirubin less than 1.5mg/dl. other known causes of ...

The multidrug resistance protein 2 (MRP2; ABCC2) is an ATPbinding cassette transporter accepting a diverse range of substrates, including glutathione, glucuronide, and sulfate conjugates of many endoand xenobiotics. MRP2 generally performs excretory or protective roles, and it is expressed on the apical domain of hepatocytes, enterocytes of the proximal small intestine, and proximal renal tubul...

objective: jaundice with indirect hyperbilirubinemia is one of the most common neonatal problems that occur in 60% of term and 80% of preterm neonates but the causes are mostly unknown. it is suggested that race plays an important role in the prevalence of hyperbilirubinemia. it is a common problem in iran that worries both parents and pediatricians. it has been found that a mutation in the ugt...

Irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11), is a potent anticancer drug that is increasingly used in chemotherapy. A frequent limiting side effect involves gastrointestinal toxicity (diarrhea), which is thought to be related to the biliary excretion of CPT-11 and its metabolites. Accordingly, the biliary excretion mechanisms for both the lactone and ...