{"title":"介孔二氧化硅给药作为华法林毒性管理的新策略:一项体外和体内研究。","authors":"Fatemeh Farjadian, Fatemeh Parsi, Reza Heidari, Khatereh Zarkesh, Hamid Reza Mohammadi, Soliman Mohammadi-Samani, Lobat Tayebi","doi":"10.34172/apb.42665","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>Amino-functionalized mesoporous silica (MS-NH<sub>2</sub>) 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-NH<sub>2</sub> 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-NH<sub>2</sub> by oral gavage. Biomarkers of organ injury were assessed in animal serum.</p><p><strong>Results: </strong>The MS-NH<sub>2</sub> was relatively uniform, spherical with defined diameters (400 nm) and porous structure. Synthesized particles had a large surface area (1015 m<sub>2</sub> g<sup>-1</sup>) 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-NH<sub>2</sub> in mice poisoned with warfarin caused a significant difference (<i>P</i><0.05) in the International Normalized Ratio (INR) and prothrombin time (PT). Moreover, the warfarin with MS-NH<sub>2</sub> group demonstrated a notable decrease in biomarkers associated with tissue damage, such as bilirubin, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).</p><p><strong>Conclusion: </strong>The results confirm that MS-NH<sub>2</sub> administration can be an effective treatment for warfarin toxicity and could potentially mitigate the adverse effects of warfarin poisoning.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"14 4","pages":"883-891"},"PeriodicalIF":3.1000,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970487/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mesoporous Silica Administration as a New Strategy in the Management of Warfarin Toxicity: An In-Vitro and In-Vivo Study.\",\"authors\":\"Fatemeh Farjadian, Fatemeh Parsi, Reza Heidari, Khatereh Zarkesh, Hamid Reza Mohammadi, Soliman Mohammadi-Samani, Lobat Tayebi\",\"doi\":\"10.34172/apb.42665\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>Amino-functionalized mesoporous silica (MS-NH<sub>2</sub>) 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-NH<sub>2</sub> 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-NH<sub>2</sub> by oral gavage. Biomarkers of organ injury were assessed in animal serum.</p><p><strong>Results: </strong>The MS-NH<sub>2</sub> was relatively uniform, spherical with defined diameters (400 nm) and porous structure. Synthesized particles had a large surface area (1015 m<sub>2</sub> g<sup>-1</sup>) 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-NH<sub>2</sub> in mice poisoned with warfarin caused a significant difference (<i>P</i><0.05) in the International Normalized Ratio (INR) and prothrombin time (PT). Moreover, the warfarin with MS-NH<sub>2</sub> group demonstrated a notable decrease in biomarkers associated with tissue damage, such as bilirubin, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).</p><p><strong>Conclusion: </strong>The results confirm that MS-NH<sub>2</sub> administration can be an effective treatment for warfarin toxicity and could potentially mitigate the adverse effects of warfarin poisoning.</p>\",\"PeriodicalId\":7256,\"journal\":{\"name\":\"Advanced pharmaceutical bulletin\",\"volume\":\"14 4\",\"pages\":\"883-891\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970487/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced pharmaceutical bulletin\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.34172/apb.42665\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced pharmaceutical bulletin","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.34172/apb.42665","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Mesoporous Silica Administration as a New Strategy in the Management of Warfarin Toxicity: An In-Vitro and In-Vivo Study.
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.
Methods: 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.
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.