Effects of lipopolysaccharide on P-glycoprotein expression and activity in the liver and kidneys

Kato, Ryuichi; Moriguchi, Jun; Irie, Takako; Nakagawa, Machiko; Kusukawa, Yugo; Matsumura, Hitoshi; Ijiri, Yoshio; Tanaka, Kazuhiko

doi:10.1016/j.ejphar.2010.03.024

Cited by 10 publications

(10 citation statements)

References 12 publications

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“…This hypothesis is supported by a previous report [33] . Rho123, a typical substrate of P-GP, has been widely used as an index of P-GP mediated transport in in vitro and in vivo studies [34][35][36][37][38][39][40] . In the present study, Rho123 also served as a marker for evaluating P-GP function.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

et al. 2011

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Aim: To investigate the changes of expression and function of P-glycoprotein (P-GP) in cerebral cortex, hippocampus, liver, intestinal mucosa and kidney of streptozocin-induced diabetic rats. Methods: Diabetic rats were prepared via a single dose of streptozocin (65 mg/kg, ip). Abcb1/P-GP mRNA and protein expression levels in tissues were evaluated using quantitative real time polymerase chain reaction (QRT-PCR) analysis and Western blot, respectively. P-GP function was investigated via measuring tissue-to-plasma concentration ratios and body fluid excretion percentages of rhodamine 123. Results: In 5-and 8-week diabetic rats, Abcb1a mRNA levels were significantly decreased in cerebral cortices and intestinal mucosa, but dramatically increased in hippocampus and kidney. In liver, the level was increased in 5-week diabetic rats, and decreased in 8-week diabetic rats. Abcb1b mRNA levels were increased in cerebral cortex, hippocampus and kidney, but reduced in liver and intestinal mucosa in the diabetic rats. Western blot results were in accordance with the alterations of Abcb1a mRNA levels in most tissues examined. P-GP activity was markedly decreased in most tissues of diabetic rats, except kidney tissues. Conclusion: Alterations in the expression and function of Abcb1/P-GP under diabetic conditions are tissue specific, Abcb1 specific and diabetic duration-dependent.

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Section: Discussionmentioning

confidence: 99%

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

et al. 2011

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“…There are known differences in P-gp activity and expression in the kidneys and liver, pointing to a possible involvement of P-gp in QD elimination. 51 We used two pharmacological modulators of P-gp activity, rifampin and elacridar, to investigate the role of P-gp in QD elimination. Rifampin is a P-gp inducer known to increase P-gp activity through mechanisms that are still poorly understood.…”

Section: Articlementioning

confidence: 99%

Short Ligands Affect Modes of QD Uptake and Elimination in Human Cells

et al. 2011

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In order to better understand nanoparticle uptake and elimination mechanisms, we designed a controlled set of small, highly fluorescent quantum dots (QDs) with nearly identical hydrodynamic size (8À10 nm) but with varied short ligand surface functionalization. The properties of functionalized QDs and their modes of uptake and elimination were investigated systematically by asymmetrical flow fieldÀflow fractionation (AF4), confocal fluorescence microscopy, flow cytometry (FACS), and flame atomic absorption (FAA). Using specific inhibitors of cellular uptake and elimination machinery in human embryonic kidney cells (Hek 293) and human hepatocellular carcinoma cells (Hep G2), we showed that QDs of the same size but with different surface properties were predominantly taken up through lipid raft-mediated endocytosis, however, to significantly different extents. The latter observation infers the contribution of additional modes of QD internalization, which include X-AG cysteine transporter for cysteine-functionalized QDs (QD-CYS).We also investigated putative modes of QD elimination and established the contribution of P-glycoprotein (P-gp) transporter in QD efflux. Results from these studies show a strong dependence between the properties of QD-associated small ligands and modes of uptake/elimination in human cells.

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“…LPS influences the pharmacokinetics of drugs by modulating the activities of both phase I (Pan et al, 2003;Xu et al, 2006) and phase II (Alkharfy et al, 2008;Richardson et al, 2006) drug-metabolizing enzymes. LPS also modulates drug transporters such as organic cation transporters (Heemskerk et al, 2008) and p-glycoprotein (P-gp) distributed in the blood brain barrier (Salkeni et al, 2009), liver (Kato et al, 2010), intestine (Mishra et al, 2008), and kidney (Hartmann et al, 2005). Given that Rhizoma coptidis alkaloids are substrates of P-gp (Zhang et al, 2011) and are mainly eliminated via metabolism , LPS is assumed to influence the acute toxicity of the Rhizoma coptidis extract by changing the pharmacokinetics of this TCM.…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide increased the acute toxicity of the Rhizoma coptidis extract in mice by increasing the systemic exposure to Rhizoma coptidis alkaloids

Gao

et al. 2011

Journal of Ethnopharmacology

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Effects of lipopolysaccharide on P-glycoprotein expression and activity in the liver and kidneys

Cited by 10 publications

References 12 publications

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

Tissue-specific alterations in expression and function of P-glycoprotein in streptozotocin-induced diabetic rats

Short Ligands Affect Modes of QD Uptake and Elimination in Human Cells

Lipopolysaccharide increased the acute toxicity of the Rhizoma coptidis extract in mice by increasing the systemic exposure to Rhizoma coptidis alkaloids

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