Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB
Liver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cir...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/3019794 |
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| author | José Roberto Macías-Pérez Bruno Jesús Vázquez-López Martin Humberto Muñoz-Ortega Liseth Rubí Aldaba-Muruato Sandra Luz Martínez-Hernández Esperanza Sánchez-Alemán Javier Ventura-Juárez |
| author_facet | José Roberto Macías-Pérez Bruno Jesús Vázquez-López Martin Humberto Muñoz-Ortega Liseth Rubí Aldaba-Muruato Sandra Luz Martínez-Hernández Esperanza Sánchez-Alemán Javier Ventura-Juárez |
| author_sort | José Roberto Macías-Pérez |
| collection | DOAJ |
| description | Liver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cirrhosis. However, several studies suggest that the toxicity generated by metabolism of these antagonists would hinder its use in cirrhotic patients. In addition, liver fibrosis may be associated with a decrease of the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and the overregulation of the proinflammatory pathway of nuclear factor kappa B (NF-κB). Therefore, in the present work, the capacity of doxazosin (α1 antagonist), carvedilol (nonselective beta-adrenoceptor blocker with alpha 1-blocking properties), and curcumin (antioxidant and anti-inflammatory compound) to reverse liver cirrhosis and studying the possible modulation of Nrf-2 and NF-κB were evaluated. Hamsters received CCl4 for 20 weeks, and then treatments were immediately administered for 4 weeks more. The individual administration of doxazosin or carvedilol showed less ability to reverse cirrhosis in relation to concomitantly curcumin administration. However, the best effect was the combined effect of doxazosin, carvedilol, and curcumin, reversing liver fibrosis and decreasing the amount of collagen I (Sirius red stain) without affecting the morphology of hepatocytes (hematoxylin and eosin stain), showing normal hepatic function (glucose, albumin, AST, ALT, total bilirubin, and total proteins). In addition, carvedilol treatment and the combination of doxazosin with curcumin increased Nrf-2/NF-κB mRNA ratio and its protein expression in the inflammatory cells in the livers, possibly as another mechanism of hepatoprotection. Therefore, these results suggest for the first time that α/β adrenergic blockers with curcumin completely reverse hepatic damage, possibly as a result of adrenergic antagonism on HSC and conceivably by the increase of Nrf-2/NF-κB mRNA ratio. |
| format | Article |
| id | doaj-art-fc82d793dfc54143aee11827cda565cd |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-fc82d793dfc54143aee11827cda565cd2025-02-03T01:26:09ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/30197943019794Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κBJosé Roberto Macías-Pérez0Bruno Jesús Vázquez-López1Martin Humberto Muñoz-Ortega2Liseth Rubí Aldaba-Muruato3Sandra Luz Martínez-Hernández4Esperanza Sánchez-Alemán5Javier Ventura-Juárez6Química Clínica, Unidad Académica Multidisciplinaria Zona Huasteca, Universidad Autónoma de San Luis Potosí, Ciudad Valles, SLP, MexicoDepartamento de Química, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, AGS, MexicoDepartamento de Química, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, AGS, MexicoQuímica Clínica, Unidad Académica Multidisciplinaria Zona Huasteca, Universidad Autónoma de San Luis Potosí, Ciudad Valles, SLP, MexicoDepartamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, AGS, MexicoDepartamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, AGS, MexicoDepartamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, AGS, MexicoLiver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cirrhosis. However, several studies suggest that the toxicity generated by metabolism of these antagonists would hinder its use in cirrhotic patients. In addition, liver fibrosis may be associated with a decrease of the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and the overregulation of the proinflammatory pathway of nuclear factor kappa B (NF-κB). Therefore, in the present work, the capacity of doxazosin (α1 antagonist), carvedilol (nonselective beta-adrenoceptor blocker with alpha 1-blocking properties), and curcumin (antioxidant and anti-inflammatory compound) to reverse liver cirrhosis and studying the possible modulation of Nrf-2 and NF-κB were evaluated. Hamsters received CCl4 for 20 weeks, and then treatments were immediately administered for 4 weeks more. The individual administration of doxazosin or carvedilol showed less ability to reverse cirrhosis in relation to concomitantly curcumin administration. However, the best effect was the combined effect of doxazosin, carvedilol, and curcumin, reversing liver fibrosis and decreasing the amount of collagen I (Sirius red stain) without affecting the morphology of hepatocytes (hematoxylin and eosin stain), showing normal hepatic function (glucose, albumin, AST, ALT, total bilirubin, and total proteins). In addition, carvedilol treatment and the combination of doxazosin with curcumin increased Nrf-2/NF-κB mRNA ratio and its protein expression in the inflammatory cells in the livers, possibly as another mechanism of hepatoprotection. Therefore, these results suggest for the first time that α/β adrenergic blockers with curcumin completely reverse hepatic damage, possibly as a result of adrenergic antagonism on HSC and conceivably by the increase of Nrf-2/NF-κB mRNA ratio.http://dx.doi.org/10.1155/2019/3019794 |
| spellingShingle | José Roberto Macías-Pérez Bruno Jesús Vázquez-López Martin Humberto Muñoz-Ortega Liseth Rubí Aldaba-Muruato Sandra Luz Martínez-Hernández Esperanza Sánchez-Alemán Javier Ventura-Juárez Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB Journal of Immunology Research |
| title | Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB |
| title_full | Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB |
| title_fullStr | Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB |
| title_full_unstemmed | Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB |
| title_short | Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB |
| title_sort | curcumin and α β adrenergic antagonists cotreatment reverse liver cirrhosis in hamsters participation of nrf 2 and nf κb |
| url | http://dx.doi.org/10.1155/2019/3019794 |
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