Experimental Model of Subclinical Vitamin K Deficiency

• Main Authors: Silvia Gancheva, Martina Kitanova, Peter Ghenev, Maria Zhelyazkova-Savova
• Format: Article
• Language: English
• Published: Pensoft Publishers 2020-06-01
• Series: Folia Medica
• Subjects: osteocalcin; rats; vascular calcification; warfari
• Online Access: https://foliamedica.bg/article/47510/download/pdf/

Introduction: Vitamin K (VK) is a co-factor in the post-translational gamma glutamic carboxylation of Gla-proteins. VK-dependent coagulation factors are carboxylated in the liver by VK1. Osteocalcin and Matrix-Gla protein (MGP) are carboxylated in extrahepatic tissues by VK2. A model of VK deficiency would be suitable for studying extrahepatic Gla-proteins provided that severe bleeding is prevented.Aim: The aim of this work was to adapt an established protocol of vascular calcification by warfarin-induced inactivation of MGP as a calcification inhibitor, in an attempt to create a broader state of subclinical VK deficiency and to verify its safety.Materials and methods: Two consecutive experiments, each lasting 4 weeks, were required to modify the dosing schedule of warfa­rin and VK1 and to adapt it to the Wistar rats used. The original high doses of warfarin used initially had to be halved and the protective dose of VK1 to be doubled, in order to avoid treatment-induced hemorrhagic deaths. The second experiment aimed to confirm the efficacy and safety of the modified doses.To verify the VK deficiency, blood vessels were examined histologically for calcium deposits and serum osteocalcin levels were mea­sured.Results: The original dosing schedule induced VK deficiency, manifested by arterial calcifications and dramatic changes in carboxyl­ated and uncarboxylated osteocalcin. The modified dosing regimen caused similar vascular calcification and no bleeding.Conclusion: The modified protocol of carefully balanced warfarin and VK1 doses is an effective and safe way to induce subclinical VK deficiency that can be implemented to investigate VK-dependent proteins like osteocalcin.