Optimization of ferric chloride induced thrombosis model in rats: effect of anti-platelet and anti-coagulant drugs

Abstract

Numerous studies on various animal species, with variability in the site of application and the concentration of ferric chloride (FeCl₃) to induce intravascular thrombosis has prompted us to undertake the present study to obtain a threshold concentration of FeCl₃ and validate this model by clinically used anti-thrombotic drugs. A small piece of filter paper, soaked in FeCl₃ solution (10, 20, 40, 60 or 80%, w/v), was topically applied on the carotid artery of SD rats to measure the time till occlusion (TTO), to ascertain 20% as an optimal FeCl₃ concentration. Anti-platelet drugs, aspirin (30 mg/kg), ticlopidine (200 mg/kg) or clopidogrel (30 mg/kg), administered by oral route for 3 days (once daily) or 4 h (single dose) prior to the induction of thrombosis, showed the rank-order: clopidogrel > ticlopidine > aspirin based on TTO by 20% FeCl₃. Anti-coagulant drug, heparin (10 U/kg, 30 U/kg and 100 U/kg, i.v) increased TTO in a dose dependent manner (18 ± 1.7, 22 ± 0.9 and 27 ± 3.9 min respectively), while warfarin treated rats at 0.1 mg/kg or 0.3 mg/kg, (po for 5 days), exhibited TTO augmentation to 85 ± 11.8 and 120 ± 0 min respectively. The results obtained indicate that among the drugs tested warfarin and clopidogrel were most efficacious in this model, while rank order of the other anti-thrombotic drugs were heparin > ticlopidine > aspirin. The present study thus provides a simple, reproducible and well controlled methodology to induce thrombosis in rats by the topical application of 20% FeCl₃ to assess the efficacy of new anti-thrombotic agents.