Preserved cytosolic and synthetic liver function in jaundice of severe extrahepatic infection

Pirovino, M; Meister, F.; Rubli, E; Karlaganis, Georg

doi:10.1016/0016-5085(89)90531-3

Cited by 36 publications

(17 citation statements)

References 23 publications

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“…This alternate vectoral excretion from hepatocyte to blood may serve as a second compensatory mechanism to reduce hepatic exposure to bile acids as well as other toxic biliary constituents during sepsis. Clinically, jaundice is common among septic patients; however, the circulating bilirubin in these patients is predominantly present in the relatively nontoxic conjugated forms (Pirovino et al, 1989). To appear in the circulating blood, conjugated bilirubin requires an active transport process across the sinusoidal membrane out of the hepatocyte.…”

Section: Fig 7 Pretreatment Effects On Hepatic Oct and Oat Mrna Expmentioning

confidence: 99%

LIPOPOLYSACCHARIDE-MEDIATED REGULATION OF HEPATIC TRANSPORTER mRNA LEVELS IN RATS

Cherrington¹,

Slitt²,

Li³

et al. 2004

Drug Metab Dispos

138

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ABSTRACT:The function of hepatic transporters is to move organic substances across sinusoidal and canalicular membranes. During extrahepatic cholestasis, transporters involved in the movement of substances from blood to bile, such as sodium/taurocholate-cotransporting polypeptide (Ntcp) and multidrug resistance protein 2 (Mrp2), are down-regulated, whereas others that transport chemicals from liver to blood, such as Mrp3, are up-regulated. Unlike extrahepatic cholestasis, where transporter expression responds to the stress of accumulating bile constituents, lipopolysaccharide (LPS)-induced intrahepatic cholestasis may be directly caused by alterations in transporter expression. The aim of this study was to quantitatively determine the effect of LPS on transporter expression and study the mechanism(s) by which LPS alters mRNA levels of major hepatic transporters in Sprague-Dawley rats. Hepatic mRNA levels of Mrp2, Mrp6, multiple drug resistance protein 1a (Mdr1a), organic anion-transporting polypeptide 1 (Oatp1), Oatp2, Oatp4, Ntcp, bile salt export pump, organic cation transporter 1 (Oct1), and organic anion transporter 3 (Oat3) were dramatically decreased, beginning approximately 6 h after LPS administration, whereas Mrp5 and Oat2 levels were unchanged. In contrast, LPS increased mRNA levels of Mrp1, Mrp3, and Mdr1b concurrently with the down-regulated transporters. Pretreatment with dexamethasone, which decreases the release of cytokines, reversed the reduction of Mdr1a, Oatp1, Oatp2, Oct1, and Ntcp mRNA following LPS administration. Furthermore, dexamethasone pretreatment also prevented the LPS-mediated increase in Mrp1, Mrp3, and Mdr1b, whereas pretreatment with aminoguanidine or gadolinium chloride, an inhibitor of inducible nitric oxide synthetase and a Kupffer cell toxicant, respectively, had no effect on the LPSinduced changes. The concurrent repression and induction of various transporters, as well as dexamethasone abatement of both LPS-mediated repression and induction, indicates that these responses may be mediated through similar pathways.

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Section: Fig 7 Pretreatment Effects On Hepatic Oct and Oat Mrna Expmentioning

confidence: 99%

LIPOPOLYSACCHARIDE-MEDIATED REGULATION OF HEPATIC TRANSPORTER mRNA LEVELS IN RATS

Cherrington¹,

Slitt²,

Li³

et al. 2004

Drug Metab Dispos

138

View full text Add to dashboard Cite

show abstract

“…The most plausible explanation for that was the worsening of preexisting CIDP which was evident in the nerve conduction studies. This was different to the development of Guillain-Barre Syndrome which was previously reported as a rare complication of melioidosis [9,10]. Normal MRI spine excluded the cord compression related to abscess formation [13].…”

Section: Discussionmentioning

confidence: 54%

A Case of Melioidosis with Multiple Lung Abscesses, Intrahepatic Cholestasis and Hepatic Encephalopathy

Palangasinghe¹

2017

J Bacteriol Mycol

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“…patients. 1 Endotoxin, a major exogenous product of bacteria, causes similar morphological and functional alterations in MATERIALS AND METHODS the liver. 2 Because the addition of endotoxin to isolated hepatocytes has no effect on the release of aspartate transaminase Chemicals.…”

Section: Lps and By Aminoguanidine (Amg) (5 Mg/kg/h) Plus Lpsmentioning

confidence: 99%

Role of nitric oxide in oxygen transport in rat liver sinusoids during endotoxemia

et al. 1997

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tor, tumor necrosis factor, and other cytokines. 4 All of these To evaluate the role of nitric oxide (NO) in hepatic micromediators may be involved in the pathogenesis of liver injury, circulation and liver injury during endotoxemia, we studied probably initiated by microvascular disturbance caused by O 2 transport in the hepatic microcirculation of endotoxinleukocyte adhesion to endothelial cells in the hepatic sinuinfused rats. Rats were continuously infused with Escherichia soids. [5][6][7] Nitric oxide (NO) also increases during endotoxcoli lipopolysaccharide (LPS) (0.8 mg/kg/h) for 7 hours. LPS emia 8,9 and sepsis, 10 produced by Kupffer cells, macrophages, increased the plasma levels of NO 0 2 / NO 0 3 and aspartate hepatocytes, and sinusoidal endothelial cells. 9 Overproductransaminase (AST), and decreased the bile flow rate and tion of NO plays a toxic role in septic shock. 11 Peroxynitrite hepatic adenosine triphosphate (ATP) level. Hepatic microcirgenerated from superoxide and NO may be involved in sevculation was evaluated by two methods: reflectance spectroeral types of tissue injury. 12,13 On the contrary, NO attenuates photometry showed a decrease in the oxygenation of hemoglohepatic injury during endotoxemia. 14-17 Thus, the roles of bin (Hb) in the liver, and dual-spot microspectroscopy NO in endotoxemia are controversial. Nishida et al. recently indicated that LPS administration decreased blood velocity, reported that inhibition of NO synthesis in endotoxemia led the oxygenation of Hb, and O 2 release from sinusoids to hepato an increase in the leukocytes adhering to the sinusoidal tocytes. The observed decreases in the O 2 transport paramewall and a decrease in the number of sinusoids displaying ters were prominent in pericentral sinusoids. All of these blood flow. 5 These results imply a deterioration of O 2 transphenomena were further aggravated by the administration of port in hepatic microcirculation; however, there has as yet N w -nitro-L-arginine methyl ester (L-NAME) (5 mg/kg/h) plus been no experimental evidence of this. LPS, and by aminoguanidine (AMG) (5 mg/kg/h) plus LPS,Dual-spot microspectroscopy is useful for evaluating heand these could be reversed by the concomitant administrapatic microcirculation to quantify sinusoidal O 2 transport tion of L-arginine (L-Arg) (100 mg/kg/h). These results suggest parameters such as red blood cell velocity, intrasinusoidal that deterioration of hepatic oxygen transport and liver funchemoglobin (Hb) concentration, Hb oxygenation, and the tion induced by endotoxin can be ameliorated by NO. (HEPArate of O 2 transfer from sinusoids to hepatocytes. 18 In the TOLOGY 1997;26:336-342.) present study, we used this method to quantitatively study periportal and pericentral sinusoidal O 2 transport in endoCholestatic liver injury is commonly observed in septic toxin-infused rat livers. patients. 1 Endotoxin, a major exogenous product of bacteria, causes similar morphological and functional alterations in MATERIALS AND METHODS the liver. 2 Because the addit...

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Preserved cytosolic and synthetic liver function in jaundice of severe extrahepatic infection

Cited by 36 publications

References 23 publications

LIPOPOLYSACCHARIDE-MEDIATED REGULATION OF HEPATIC TRANSPORTER mRNA LEVELS IN RATS

LIPOPOLYSACCHARIDE-MEDIATED REGULATION OF HEPATIC TRANSPORTER mRNA LEVELS IN RATS

A Case of Melioidosis with Multiple Lung Abscesses, Intrahepatic Cholestasis and Hepatic Encephalopathy

Role of nitric oxide in oxygen transport in rat liver sinusoids during endotoxemia

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