Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas
Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue ur...
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MDPI AG
2020-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/4/237 |
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| author | Yu-Chung Shih Chih-Cheng Wu Shen-Chih Wang Jun-Yang Liou Po-Hsun Huang Der-Cherng Tarng |
| author_facet | Yu-Chung Shih Chih-Cheng Wu Shen-Chih Wang Jun-Yang Liou Po-Hsun Huang Der-Cherng Tarng |
| author_sort | Yu-Chung Shih |
| collection | DOAJ |
| description | Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFβ was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency. |
| first_indexed | 2024-03-10T20:36:24Z |
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| id | doaj.art-fc5691a5ce4d4537a014be6bf7c7c20b |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T20:36:24Z |
| publishDate | 2020-04-01 |
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| series | Toxins |
| spelling | doaj.art-fc5691a5ce4d4537a014be6bf7c7c20b2023-11-19T21:00:41ZengMDPI AGToxins2072-66512020-04-0112423710.3390/toxins12040237Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous FistulasYu-Chung Shih0Chih-Cheng Wu1Shen-Chih Wang2Jun-Yang Liou3Po-Hsun Huang4Der-Cherng Tarng5Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, TaiwanCardiovascular Center, National Taiwan University Hospital, Hsinchu Branch, Hsinchu 30059, TaiwanDepartment of Anesthesiology, Taipei Veterans General Hospital, Taipei 11217, TaiwanInstitute of Cellular and System Medicine, National Health Research Institutes, Zhunan 35053, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei 11221, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei 11221, TaiwanChronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFβ was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.https://www.mdpi.com/2072-6651/12/4/237arteriovenous fistulacharcoal adsorbentindoxyl sulfateneointimauremic toxin |
| spellingShingle | Yu-Chung Shih Chih-Cheng Wu Shen-Chih Wang Jun-Yang Liou Po-Hsun Huang Der-Cherng Tarng Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas Toxins arteriovenous fistula charcoal adsorbent indoxyl sulfate neointima uremic toxin |
| title | Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas |
| title_full | Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas |
| title_fullStr | Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas |
| title_full_unstemmed | Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas |
| title_short | Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas |
| title_sort | oral charcoal adsorbents attenuate neointima formation of arteriovenous fistulas |
| topic | arteriovenous fistula charcoal adsorbent indoxyl sulfate neointima uremic toxin |
| url | https://www.mdpi.com/2072-6651/12/4/237 |
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