Strain differences in intestinal toxicity of warfarin in rats.
Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5mg/l) led to mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values of prothrombin time were noted at low WF dose (0.35mg/l) in the former strain. Leukocyte infiltration in intestine noted at this dose in both strains was associated with oxidative injury and more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats, represent different strategies to protect vulnerable intestine from harmful immune responses.
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
Ivana
I
Mirkov
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
Aleksandra
A
Popov Aleksandrov
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
Marina
M
Ninkov
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
Dina
D
Mileusnic
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
Jelena
J
Demenesku
Institute for Pathology, Military Medical Academy, 17 Crnotravska, 11000 Belgrade, Serbia.
Lidija
L
Zolotarevski
Institute for Medical Biochemistry, Military Medical Academy, 17 Crnotravska, 11000 Belgrade, Serbia.
Vesna
V
Subota
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia.
Debora
D
Stefik
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia; Institute of Zoology, Faculty of Biology, University of Belgrade,16 Studentski trg, 11000 Belgrade, Serbia.
Dragan
D
Kataranovski
Immunotoxicology group, Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, 142 Bulevar despota Stefana, 11000 Belgrade, Serbia; Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 16 Studentski trg, 11000 Belgrade, Serbia. Electronic address: milena@ibiss.bg.ac.rs.
Milena
M
Kataranovski
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D011517:Prothrombin Time; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014859:Warfarin / Q000633:toxicity*
D000925:Anticoagulants; D016207:Cytokines; D014859:Warfarin
Albino Oxford (AO) and Dark agouti (DA) rats; Intestinal injury; Mesenteric lymph nodes; Oral warfarin administration