The production of disseminated intravascular coagulation (DIC) by spaced injections of endotoxin in nonpregnant, normolipaemic rats

Kúnz, F; R, Constantini; Semenitz, E; Mikuz, Gregor; Schmalzl, F.; Holzknecht, F

doi:10.1016/0049-3848(78)90090-7

Cited by 5 publications

(1 citation statement)

References 8 publications

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“…In addition, the concentration of bile salts generally increases in hepatic failure ( 33) and can be up to 40 times higher than in healthy patients ( 8, 32). In patients with elevated bile acid levels in plasma, several problems arise including impaired coagulation ( 34) and platelet function( 35), and altered ion transport in red blood cells ( 36).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity of Bile in Human Hep G2 Cells and in Primary Cultures of Rat Hepatocytes

et al. 1998

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There has been increasing interest in the development of a hepatocyte bioreactor for the treatment of acute hepatic failure; however, little is known about the effect of hepatocyte byproducts on the viability of the cells in the bioreactor environment. We investigated the effects of increasing concentrations of bile on the growth and viability of the human hepatoma cell line Hep G2 and on the cytochrome P-450 content and dependent mixed function oxidase (MFO) activities, reduced glutathione (GSH) content, and glutathione S-transferase (GST) activity of primary cultures of rat hepatocytes. Our purpose was to determine whether or not it would be necessary to pretreat the plasma from patients with acute liver failure to remove elevated bile concentrations which might be toxic to the hepatocytes in an artificial liver device. Bile was found to inhibit Hep G2 cell growth at concentrations as low as 0.1% and to decrease viability at concentrations above 0.5%. The cytochrome P-450 and GSH contents and the activities of the MFO system and of GST were decreased in the primary cultures of hepatocytes following 24 h treatment with concentrations of bile at and above 0.5%. The MFO activities associated with different cytochrome P-450 isoenzymes decreased to different extents in the presence of bile with the O-dealkylation of pentoxyresorufin being more labile than that of ethoxyresorufin. Our data indicate that elevated bile concentrations are cytotoxic to liver cells, and it may be necessary to pretreat patient plasma to decrease its bile content to protect the cells during the clinical operation of a hepatocyte bioreactor device.

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Section: Discussionmentioning

confidence: 99%

Cytotoxicity of Bile in Human Hep G2 Cells and in Primary Cultures of Rat Hepatocytes

et al. 1998

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Endotoxin, prostaglandins and renal fibrin deposition in obstructive jaundice

Fletcher¹,

Westwick²,

Vv³

1982

Journal of British Surgery

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The delayed clearance of endotoxins in obstructive jaundice may cause renal impairment by inducing renal vasoconstriction and glomerular fibrin deposition as a consequence of intravascular coagulation. As endotoxins activate arachidonic acid metabolism we have examined the effects of selective inhibitors on mortality, plasma TXB2 and 6-oxo-PGF1 alpha production and renal fibrin deposition in rats with obstructive jaundice following endotoxin administration. Jaundiced rats had a high mortality following endotoxin--58 per cent at 4 h and 83 per cent at 24 h. Pretreatment with indomethacin 3 mg/kg i.p., dazoxiben 3 mg i.p. or prostacyclin 300 ng/kg i.v. produced significant improvements in survival. Endotoxaemia was associated with significant elevations of plasma TXB2 and early inhibition of plasma 6-oxo-PGF1 alpha generation. Renal fibrin deposition, assessed using indirect immunofluorescence and a 125I-labelled fibrinogen uptake ratio, occurred in jaundiced kidneys following endotoxin and could be prevented using indomethacin, dazoxiben and prostacylin. These results suggest that endotoxin-induced TXA2 production can cause renal fibrin deposition in obstructive jaundice, thus contributing in the pathogenesis of the renal impairment.

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Renal dysfunction in obstructive jaundice

Fogarty

Parks

Rowlands

et al. 1995

Journal of British Surgery

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The association between renal dysfunction and obstructive jaundice is well established. Despite a substantial number of clinical reviews and prospective studies, the exact incidence and extent of the problem has not been determined accurately. Various pathogenic mechanisms and therapeutic strategies have been proposed but renal dysfunction remains a persistent problem in hepatobiliary practice. The intention of this review is to determine the current extent of the problem, outline the proposed pathophysiological mechanisms and assess the current therapeutic options.

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The production of disseminated intravascular coagulation (DIC) by spaced injections of endotoxin in nonpregnant, normolipaemic rats

Cited by 5 publications

References 8 publications

Cytotoxicity of Bile in Human Hep G2 Cells and in Primary Cultures of Rat Hepatocytes

Cytotoxicity of Bile in Human Hep G2 Cells and in Primary Cultures of Rat Hepatocytes

Endotoxin, prostaglandins and renal fibrin deposition in obstructive jaundice

Renal dysfunction in obstructive jaundice

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