Effect of Cadmium on Bromosulfophthalein Kinetics in the Isolated Perfused Rat Liver System

Soto, Ana M.

doi:10.1093/toxsci/69.2.460

Cited by 13 publications

(14 citation statements)

References 21 publications

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“…4, P Ͻ 0.05 vs. IgG ϩ LPS/Gal, n ϭ 5-7). Mice were injected with BSP to analyze the excretory function of the liver in vivo (23). We found that BSP excretion in control mice was 7.6 Ϯ 0.3 mg/ml and that LPS treatment decreased excretion of BSP down to 1.3 Ϯ 0.5 mg/ml, corresponding to an 83% reduction ( Fig.…”

Section: Resultsmentioning

confidence: 86%

Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice

Laschke

Menger²,

Wang³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Thorlacius H. Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice. Am J Physiol Gastrointest Liver Physiol 292: G1396 -G1402, 2007. First published January 25, 2007 doi:10.1152/ajpgi.00539.2006.-Cholestasis is a major complication in sepsis although the underlying mechanisms remain elusive. The aim of this study was to evaluate the role of P-selectin and leukocyte recruitment in endotoxemia-associated cholestasis. C57BL/6 mice were challenged intraperitoneally with endotoxin (0.4 mg/kg), and 6 h later the common bile duct was cannulated for determination of bile flow and biliary excretion of bromosulfophthalein. Mice were pretreated with an anti-P-selectin antibody or an isotype-matched control antibody. Leukocyte infiltration was determined by measuring hepatic levels of myeloperoxidase. Tumor necrosis factor-␣ and CXC chemokines in the liver was determined by ELISA. Liver damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. Apoptosis was quantified morphologically by nuclear condensation and fragmentation using Hoechst 33342 staining. Endotoxin induced a significant inflammatory response with increased TNF-␣ and CXC chemokine concentrations, leukocyte infiltration, liver enzyme release, and apoptotic cell death. This response was associated with pronounced cholestasis indicated by a Ͼ70% decrease of bile flow and biliary excretion of bromosulfophthalein. Immunoneutralization of P-selectin significantly attenuated endotoxin-induced leukocyte infiltration reflected by a Ͼ60% reduction of hepatic myeloperoxidase levels. Interference with P-selectin decreased endotoxin-mediated hepatocellular apoptosis and necrosis, but did not affect hepatic levels of tumor necrosis factor-␣ and CXC chemokines. Of interest, inhibition of P-selectin restored bile flow and biliary excretion of bromosulfophthalein to normal levels in endotoxin-challenged animals. Our study demonstrates for the first time that P-selectin-mediated recruitment of leukocytes, but not the local production of proinflammatory mediators, is the primary cause of cholestasis in septic liver injury.

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Section: Resultsmentioning

confidence: 86%

Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice

Laschke

Menger²,

Wang³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Thus, we hypothesize that chronic exposure to Cd in fish may disturb BA transport, triggering an accumulation of BAs in the hepatocytes. In support of this hypothesis, it has been shown that Cd causes a rapid decrease in bile flow and complete cholestasis in isolated perfused rat livers (Soto et al 2002). Moreover, cholestasis, by reducing bile flow, triggers malabsorption of dietary retinoids (de Vriese et al 2001;Weiss et al 2010).…”

Section: Retinol and Biliary Acid Metabolismmentioning

confidence: 92%

Effects of chronic metal exposure on wild fish populations revealed by high-throughput cDNA sequencing

et al. 2011

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Given the inherent variability of aquatic systems, predicting the in situ effects of contaminants on such ecosystems still represents a major challenge for ecotoxicology. In this context, transcriptomic tools can help identify and investigate the mechanisms of toxicity beyond the traditional morphometric, physiological and population-level endpoints. In this study, we used the 454 sequencing technology to examine the in situ effects of chronic metal (Cd, Cu) exposure on the yellow perch (Perca flavescens) transcriptome. Total hepatic mRNA from fish sampled along a polymetallic gradient was extracted, reverse transcribed, labeled with unique barcode sequences and sequenced. This approach allowed us to identify correlations between the transcription level of single genes and the hepatic concentrations of individual metals; 71% of the correlations established were negative. Chronic metal exposure was thus associated with a decrease in the transcription levels of numerous genes involved in protein biosynthesis, in the immune system, and in lipid and energy metabolism. Our results suggest that this marked decrease could result from an impairment of bile acid metabolism by Cd and energy restriction but also from the recruitment of several genes involved in epigenetic modifications of histones and DNA that lead to gene silencing.

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“…Hepatic clearance was considered another parameter of hepatic function 35, 36. Thirty minutes after the onset of the perfusion (t 30 ), 1 mg BSP (Sigma Co.) was added to the perfusate.…”

Section: Methodsmentioning

confidence: 99%

“…The concentration of BSP in bile samples (t 120 ) was measured at 580 nm with a ultraviolet‐visible spectrometer. Bile BSP excretion was expressed as a percentage of perfusate content (t 120 bile/t 30 perfusate · 100) 35, 36…”

Section: Methodsmentioning

confidence: 99%

Preservation of steatotic livers in IGL-1 solution

et al. 2006

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A new Institut Georges Lopez (IGL-1) solution was used to preserve steatotic livers. Steatotic (obese [Ob]) and nonsteatotic (lean [Ln]) livers from Zü cker rats (n ϭ 16, 8 Ln and 8 Ob) were preserved for 24 hours at 4°C in University of Wisconsin (UW) or IGL-1 solution, respectively, and then perfused ex vivo for 2 hours at 37°C. Additionally, Ob and Ln livers (n ϭ 16, 8 Ln and 8 Ob) were preserved in IGL-1 plus N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Hepatic injury and function (aminotransferases, bile production, bromosulfophthalein clearance), and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion injury, such as oxidative stress, mitochondrial damage, and vascular resistance, were studied. Nitric oxide (NO) production and constitutive and inducible NO synthase were also measured. Steatotic and nonsteatotic livers preserved in IGL-1 solution showed lower transaminases, malondialdehyde, glutamate dehydrogenase levels, and higher bile production than UW-solution-preserved livers. IGL-1 solution protected against oxidative stress, mitochondrial damage and the alterations in vascular resistance associated with cold ischemia-reperfusion. Thus, at the end of reperfusion period, aspartate aminotransferase levels in steatotic livers were 281 Ϯ 6 U/L in UW vs. 202 Ϯ 10 U/L in IGL-1 solution. Glutamate dehydrogenase was 463 Ϯ 75 U/L in UW vs. 111 Ϯ 4 U/L in IGL-1 solution, and oxidative stress was 3.0 Ϯ 0.1 nmol/mg prot in UW vs. 2.0 Ϯ 0.1 nmol/mg prot in IGL-1 solution. These beneficial effects of IGL-1 solution were abolished by the addition of L-NAME, which implicates NO in the benefits of IGL-1. In conclusion, IGL-1 solution provided steatotic livers with better protection against the deleterious effects of cold ischemia-reperfusion injury than did UW solution.

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Effect of Cadmium on Bromosulfophthalein Kinetics in the Isolated Perfused Rat Liver System

Cited by 13 publications

References 21 publications

Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice

Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice

Effects of chronic metal exposure on wild fish populations revealed by high-throughput cDNA sequencing

Preservation of steatotic livers in IGL-1 solution

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