Endotoxin, prostaglandins and renal fibrin deposition in obstructive jaundice.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D002779:Cholestasis / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology* / Q000633:toxicity; D011464:Epoprostenol / Q000494:pharmacology; D004926:Escherichia coli; D005337:Fibrin / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood
D004731:Endotoxins; D007093:Imidazoles; D011453:Prostaglandins; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D005337:Fibrin; D011464:Epoprostenol; D007213:Indomethacin