0 avis
Preliminary study on the efficiency of vitamin K on hypocoagulable rats. Introduction
Archive ouverte
Edité par CCSD -
International audience. Introduction: Vitamin K are essential molecules involved in the post-transcriptional activation of some proteins called protein vitamin K dependent (PVKD). The best know PVKD are the four involved in the coagulation cascade: factor II, VII, IX and X. In mammals, vitamin K has two origins: foods and a recycling system lead by an enzyme called Vitamin K epoxide reductase complex subunit 1 (VKORC1). The vitamin K requirement is dependent of the efficiency of this enzyme [1]. The aim of our work is to block the recycling mechanism in order to evaluate the efficiency of vitamin K1 to balance the recycle system and so to better understand the vitamin K1 action. Animals and material and methods: Thirty one31 male 8 weeks-old rats (Sprague Dawley) receive per os a lethal dose of 10mg/kg (25 fold the effective dose 50) of difethialone (a VKORC1 inhibitor). 48hForty eight hours after, a 10mg./kg-1 dose of vitamin K1 was administered per os to each rat. Rats were killed at a predetermined time after vitamin K administration and blood samples were taken. To avoid an interaction with vitamin K food, rats have been fed before and during the experiment with a vitamin K devoid food. Blood samples were assessed for blood clotting time (prothrombin time) and vitamin K dependent clotting factor activities (factor II, VII, IX and X). For statistical analysis, Wilcoxon tests were performed.Results and discussion: The delay between difethialone and vitamin K1 administration have been chosen to maximize the diminution of the vitamin K dependent clotting factor activities without involving death [2]. The results of the regeneration of vitamin K dependent clotting factor activities are presented on the figure. Regeneration evolutions fitted with a sigmoidal model (Factor II R²=0.88; VII R²=0.84; IX R²=0.78; X R²=0.93). After 360 minutes, factor II and factor IX were significantly lower (P<0.05) than their basal activity level before difethialone administration (set at 100%). For all factors, a lag time was observed during the first hour after the vitamin K administration. Then, activities increased during about one hour before to stagnate. The prothrombin time was within the normal range from 120 minutes. The lag time was expected but not the stagnation and the different levels of factor activities. The difference between factors might be explained by different affinities in the post-transcriptional modification. The stop of increasing might be explained by lack of vitamin K. However, with this hypothesis the activities should decrease but they do not. This stagnation under the normal level was not described in the case of regeneration by recovery of recycling mechanism [3]. So, unrecycled vitamin K might have a different activity or affinity which leads to a new equilibrium. Conclusion: Our experiment pinpoints that the regeneration of clotting factor activities is more complex to understand. The study of the clotting factors’ regeneration might disclose some new regulation mechanisms.References: 1. Markussen MD, Heiberg A-C, Nielsen R, Leirs H. Vitamin K requirement in Danish anticoagulant-resistant Norway rats (Rattus norvegicus). Pest Manag Sci. 2003;59(8):913‑20. 2. Lefebvre S, Rannou B, Besse S, Benoit E, Lattard V. Origin of the gender differences of the natural resistance to antivitamin K anticoagulants in rats. Toxicology. 17 févr 2016;344–346:34‑41. 3. Kerins GM, MacNicoll AD. Comparison of the half-lives and regeneration rates of blood clotting factors II, VII, and X in anticoagulant-resistant and susceptible Norway rats (Rattus norvegicus Berk.). Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. mars 1999;122(3):307‑16.
Consulter en ligne
Suggestions
Du même auteur
