Document Type

Article

Publication Date

2024

DOI

10.34172/apb.42665

Publication Title

Advances Pharmaceutical Bulletin

Volume

14

Issue

4

Pages

883-891

Abstract

Purpose: Warfarin is one of the most widely used anticoagulants that functions by inhibiting vitamin K epoxide reductase. Warfarin overdose, whether intentional or unintentional, can cause life-threatening bleeding. Here, we present a novel warfarin adsorbent based on mesoporous silica that could serve as an antidote to warfarin toxicity.

Method: Amino-functionalized mesoporous silica (MS-NH₂) was synthesized based on the cocondensation method through a soft template technique followed by template removal. The prepared structure and functional group were studied by Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) checked the morphology. The capacity of MS-NH₂ in the adsorption of warfarin was evaluated in vitro, at pH = 7.4 and pH = 1.2. In vivo evaluations were performed in control and warfarin-overdosed animal models. Overdosed animals were treated with MSNH₂ by oral gavage. Biomarkers of organ injury were assessed in animal serum.

Results: The MS-NH₂ was relatively uniform, spherical with defined diameters (400 nm) and porous structure. Synthesized particles had a large surface area (1015 m2 g(-¹)) and mean pore diameter of 2.4 nm which led to considerable adsorption capacity for warfarin 1666 mg/g. In vivo studies revealed that oral administration of MS-NH₂ in mice poisoned with warfarin caused a significant difference (P < 0.05) in the International Normalized Ratio (INR) and prothrombin time (PT). Moreover, the warfarin with MS-NH₂ group demonstrated a notable decrease in biomarkers associated with tissue damage, such as bilirubin, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).

Conclusion: The results confirm that MS-NH₂ administration can be an effective treatment for warfarin toxicity and could potentially mitigate the adverse effects of warfarin poisoning.

Rights

© 2024 The Authors.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or publishers.

Original Publication Citation

Farjadian, F., Parsi, F., Heidari, R., Zarkesh, K., Mohammadi-Samani, H. R., & Tayebi, L. (2024). Mesoporous silica administration as a new strategy in the management of Warfarin toxicity: An in-vitro and in-vivo study. Advances Pharmaceutical Bulletin, 14(4), 883-891. https://doi.org/10.34172/apb.42665

ORCID

0000-0003-1947-5658 (Tayebi)

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