Endotoxin, prostaglandins and renal fibrin deposition in obstructive jaundice

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Abstract
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-PGF1α 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-PGF1α 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.
Funding Information
  • MRC Programme (973/756)