Inhibition of fibrinolytic system by liquoid (polyanetholesulfonate). A contributing factor in the liquoid-induced renal cortical necrosis.
Liquoid induces microvascular thrombosis and renal cortical necrosis in experimental animals. We hypothesized that thrombosis and renal cortical necrosis may, at least in part, result from the inhibition of the fibrinolytic system by liquoid. Effects of liquoid on plasminogen activation by rat kidney, purified human tissue plasminogen activator (TPA), urokinase, streptokinase, and on the amidolytic activities of TPA, urokinase, and plasmin were studied using chromogenic substrates and clot lysis. Liquoid had a strong inhibitory effect on the fibrinolytic system in vivo and in vitro. The inhibition was most effective at the plasminogen activation level, with activation by streptokinase being most susceptible. The demonstrated stoichiometric binding between liquoid and plasminogen, and to a lesser degree the direct inactivation of plasminogen activators and plasmin, is probably responsible for the reduction of plasminogen activation in circulation and in the kidneys.
D000818:Animals; D001557:Benzenesulfonates / Q000009:adverse effects*; D002850:Chromatography, Gel; D004789:Enzyme Activation / Q000187:drug effects; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D005342:Fibrinolysis / Q000187:drug effects*; D007673:Kidney Cortex Necrosis / Q000139:chemically induced* / Q000503:physiopathology; D008239:Lysine / Q000494:pharmacology; D008297:Male; D010958:Plasminogen / Q000037:antagonists & inhibitors; D011074:Polyanetholesulfonate / Q000009:adverse effects* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013300:Streptokinase / Q000037:antagonists & inhibitors; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D001557:Benzenesulfonates; D011074:Polyanetholesulfonate; D010958:Plasminogen; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D008239:Lysine