title: Heme oxygenase-1 inducer hemin prevents vascular thrombosis.
abstract: Hemin is a heme oxygenase-1 (HO-1) inducer which provides endogenous carbon monoxide known for playing roles in cell proliferation, inflammation or aggregation process. The objective of the current study was to examine the effect of prophylactic treatment with hemin in a thrombosis vascular model. Three groups of Wistar rats, control (n = 6), hemin (n = 6) and hemin + HO-1 inhibitor (n = 6), were used for this study. Hemin-treated animals received hemin (50 mg/kg/d; I.P.) for seven days and HO-1 inhibitor group received hemin at the same dose and SnPP IX (60 mg/kg/d; I.P.). All animals were exposed to electric stimulation of the left carotid according to Kawasaki's procedure to induce reproducible thrombus formation. The hemin treatment did not induce blood pressure disturbance. Effects of hemin on vascular thrombosis were quantified by histopathology and its influence on haemostasis was assessed by measuring prothrombin time (PT), activated partial thromboplastin time (APTT) and blood parameters at the end of treatment. The HO-1 mRNA and protein level variation were also checked out. Results showed that chronic treatment with hemin significantly (p < 0.01) reduced the vascular occlusion degree when compared to control and hemin SnPP groups with 7.2 +/- 4.6 vs. 71.1 +/- 14.7 and 74.0 +/- 8.8%, respectively. Moreover, we observed significant (p < 0.05) perturbations of blood parameters in hemin-treated and hemin-SnPP treated rats. Interestingly, hemin treatment did not significantly increase both PT and APTT. Finally, the HO-1 mRNA and protein levels were increased in hemin-treated carotid artery. In conclusion, hemin by inducing HO-1 expression may be a preventive agent against clinical disorders associated to an increased risk of thrombosis events and may limit haemorrhagic risks.
authors.affiliation: LABPART - EA 3852 - IFR135 - Université François Rabelais, Tours Cedex 1, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desbuards
authors.forename: Gaël Y
authors.initials: GY
authors.lastname: Rochefort
authors.forename: Deborah
authors.initials: D
authors.lastname: Schlecht
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Machet
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Halimi
authors.forename: Véronique
authors.initials: V
authors.lastname: Eder
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Hyvelin
authors.forename: Daniel
authors.initials: D
authors.lastname: Antier
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D002341:Carotid Artery Thrombosis / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006418:Heme / Q000096:biosynthesis; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006427:Hemin / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D010976:Platelet Count; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D008665:Metalloporphyrins; D011524:Protoporphyrins; D012333:RNA, Messenger; D006418:Heme; D006427:Hemin; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat