# Mesoporous Silica Administration as a New Strategy in the Management of Warfarin Toxicity: An In-Vitro and In-Vivo Study

## TL;DR

This study introduces mesoporous silica as a potential antidote for warfarin overdose, showing it can reduce toxicity and organ damage in animal models.

## Contribution

A novel amino-functionalized mesoporous silica is proposed as an effective adsorbent for warfarin detoxification.

## Key findings

- MS-NH2 exhibited a high warfarin adsorption capacity of 1666 mg/g in vitro.
- In vivo, MS-NH2 significantly reduced INR and PT in warfarin-overdosed mice.
- MS-NH2 lowered biomarkers of tissue damage like bilirubin, LDH, ALT, and AST.

## Abstract

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.

Amino-functionalized mesoporous silica (MS-NH2) was synthesized based on the co-condensation 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 MS-NH2 by oral gavage. Biomarkers of organ injury were assessed in animal serum.

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).

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.