Optimization of ferric chloride induced thrombosis model in rats: effect of anti-platelet and anti-coagulant drugs.
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 4h (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.
Surin
W R
WR
Cardiovascular Pharmacology Unit, Division of Pharmacology, Central Drug Research Institute, Mahatma Gandhi Road, 226001 Lucknow, CSIR, India.
Prakash
P
P
Barthwal
M K
MK
Dikshit
M
M
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000633:toxicity*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
D000925:Anticoagulants; D002712:Chlorides; D005290:Ferric Compounds; D010975:Platelet Aggregation Inhibitors; C024555:ferric chloride