New therapeutic approach in fatty liver disease associated with metabolic dysfunction
Abstract: Non-Alcoholic Fatty Liver Disease (NAFLD) is considered a clinical manifestation of Metabolic Syndrome (MS). The hepatic lipid overload generates an excesive production of reactive oxygen species inducing oxidative stress (OS), there are still no standardized studies on effe...
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2021
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/35106 |
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I10-R327-article-35106 |
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ojs |
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Universidad Nacional de Córdoba |
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I-10 |
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R-327 |
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Revista de la Facultad de Ciencias Médicas de Córdoba |
| format |
Artículo revista |
| topic |
MAFLD Metabolic Syndrome, atorvastatin metformin MAFLD Síndrome metabólico atorvastatina metformina . |
| spellingShingle |
MAFLD Metabolic Syndrome, atorvastatin metformin MAFLD Síndrome metabólico atorvastatina metformina . Castillo, TA Scribano Parada , MP Rossi, MM Blensio, S Fonseca , L Baez, MC New therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| topic_facet |
MAFLD Metabolic Syndrome, atorvastatin metformin MAFLD Síndrome metabólico atorvastatina metformina . |
| author |
Castillo, TA Scribano Parada , MP Rossi, MM Blensio, S Fonseca , L Baez, MC |
| author_facet |
Castillo, TA Scribano Parada , MP Rossi, MM Blensio, S Fonseca , L Baez, MC |
| author_sort |
Castillo, TA |
| title |
New therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| title_short |
New therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| title_full |
New therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| title_fullStr |
New therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| title_full_unstemmed |
New therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| title_sort |
new therapeutic approach in fatty liver disease associated with metabolic dysfunction |
| description |
Abstract:
Non-Alcoholic Fatty Liver Disease (NAFLD) is considered a clinical manifestation of Metabolic Syndrome (MS). The hepatic lipid overload generates an excesive production of reactive oxygen species inducing oxidative stress (OS), there are still no standardized studies on effective treatments or consensus on the appropriate drug for each patient. Assess in MS the pharmacological response of atorvastatin and metformin on levels of inflammatory and OS biomarkers and possible liver modifications. 40 Male Wistar rats were used (8 per group): (A)Control, (B)MS, C) MS+Atorvastatin, D) MS+Metformin, E) MS+Atorvastatin+Metformin. MS was induced by 10% fructose for 6 week. The inflammatory and OS state were verify by Fibrinogen (mg/dL), Nitric oxide (NO)(µM) and superoxide dismutase (SOD)(U/mL) by means of spectrophotometry. The liver tissue was analyzed by optical microscopy(OM). ANOVA and hotelling as a post hoc test, p significance level<0.05. Fibrinogen concentration increased in (B)(288.83±6.8) with respect to (A)(203.33±6.8)(p<0.001), and in groups (C)(196±7.45), (D)(242±7.45) and (E)(104,33±6,8) showed significant regression of hyperfibrinogenemia (p<0.001). Levels of NO significantly decreased in (B)(14.76±1.86) compared to (A)(27.09±1.95)(p<0.001) and normalized their levels in the groups (C)(25.48±2.06), (D)(22.2±2,33) and (E)(31.25±2,18)(p<0,001). SOD activity in (B)(178.64±10.23) increased significantly contrasted with (A)(134.5±10.73)(p<0.001), (D)(195.71±12,82) and (E)(222,17±15.17)(p<0.001), however in group (C)(145.71±12.82) there was a significant decreased from (B)(p<0.001). In the hepatic OM (B), centrilobular and sinusoidal congestion with the presence of binucleated hepatocytes and vacuolization phenomena was evidenced. Our results indicated a pro-oxidative and inflammatory state with hepatic repercussion in (B). Atorvastatin normalizing biomarkers and retrograde the liver injury. Metformin achieves the reversal of inflammation and OS with restoration of liver tissue by showing the absence of cellular and inflammatory lesions. The pharmacological combination demonstrated superior efficacy than monotherapy, each drug acting on its biological targets, achieving greater effectiveness in normalizing biochemical variables and in regression of histological lesions. The current evidence on MS shows that in the face of a complex etiopathogenic mechanism, therapeutic approaches with multiple objectives are necessary such as the implementation of these drugs instead of waiting for an ideal drug that includes all the altered molecular pathways.
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| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2021 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/35106 |
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I10-R327-article-351062024-04-15T16:19:09Z New therapeutic approach in fatty liver disease associated with metabolic dysfunction Nuevo enfoque terapéutico en la enfermedad del hígado graso asociada a disfunción metabólica A Castillo, TA Scribano Parada , MP Rossi, MM Blensio, S Fonseca , L Baez, MC MAFLD Metabolic Syndrome, atorvastatin metformin MAFLD Síndrome metabólico atorvastatina metformina . Abstract: Non-Alcoholic Fatty Liver Disease (NAFLD) is considered a clinical manifestation of Metabolic Syndrome (MS). The hepatic lipid overload generates an excesive production of reactive oxygen species inducing oxidative stress (OS), there are still no standardized studies on effective treatments or consensus on the appropriate drug for each patient. Assess in MS the pharmacological response of atorvastatin and metformin on levels of inflammatory and OS biomarkers and possible liver modifications. 40 Male Wistar rats were used (8 per group): (A)Control, (B)MS, C) MS+Atorvastatin, D) MS+Metformin, E) MS+Atorvastatin+Metformin. MS was induced by 10% fructose for 6 week. The inflammatory and OS state were verify by Fibrinogen (mg/dL), Nitric oxide (NO)(µM) and superoxide dismutase (SOD)(U/mL) by means of spectrophotometry. The liver tissue was analyzed by optical microscopy(OM). ANOVA and hotelling as a post hoc test, p significance level<0.05. Fibrinogen concentration increased in (B)(288.83±6.8) with respect to (A)(203.33±6.8)(p<0.001), and in groups (C)(196±7.45), (D)(242±7.45) and (E)(104,33±6,8) showed significant regression of hyperfibrinogenemia (p<0.001). Levels of NO significantly decreased in (B)(14.76±1.86) compared to (A)(27.09±1.95)(p<0.001) and normalized their levels in the groups (C)(25.48±2.06), (D)(22.2±2,33) and (E)(31.25±2,18)(p<0,001). SOD activity in (B)(178.64±10.23) increased significantly contrasted with (A)(134.5±10.73)(p<0.001), (D)(195.71±12,82) and (E)(222,17±15.17)(p<0.001), however in group (C)(145.71±12.82) there was a significant decreased from (B)(p<0.001). In the hepatic OM (B), centrilobular and sinusoidal congestion with the presence of binucleated hepatocytes and vacuolization phenomena was evidenced. Our results indicated a pro-oxidative and inflammatory state with hepatic repercussion in (B). Atorvastatin normalizing biomarkers and retrograde the liver injury. Metformin achieves the reversal of inflammation and OS with restoration of liver tissue by showing the absence of cellular and inflammatory lesions. The pharmacological combination demonstrated superior efficacy than monotherapy, each drug acting on its biological targets, achieving greater effectiveness in normalizing biochemical variables and in regression of histological lesions. The current evidence on MS shows that in the face of a complex etiopathogenic mechanism, therapeutic approaches with multiple objectives are necessary such as the implementation of these drugs instead of waiting for an ideal drug that includes all the altered molecular pathways. Resumen: Enfermedad del hígado graso asociada a disfunción metabólica(MAFLD, siglas inglés),es considerada una manifestación clínica del Síndrome Metabólico(SM). La sobrecarga hepática de lípidos genera producción excesiva de especies reactivas de oxígeno induciendo Estrés Oxidativo(EO), aún no hay estudios estandarizados sobre tratamientos efectivos ni consenso sobre el fármaco adecuado para cada paciente. Valorar en SM la respuesta farmacológica de atorvastatina y metformina sobre niveles de biomarcadores inflamatorios, de EO y las posibles modificaciones hepáticas. Utilizamos 40 ratas machos Wistar (n=8 por grupo): A)Control, B)SM, C)SM+Atorvastatina, D)SM+Metformina y E)SM+Atorvastatina+Metformina. SM inducido mediante fructuosa al 10% diluida en agua durante 6 semanas. Atorvastatina 0,035mg/día/rata y 1,78mg/día/rata de metformina durante 45 días. El estado inflamatorio y EO se constató por Fibrinógeno (mg/dL), óxido nítrico (NO)(µM) y superóxido dismutasa(SOD)(U/mL) por espectrofotometría. Se analizó histología hepática por microscopía óptica(MO). ANOVA y Hotelling como test post-hoc, significación p<0.05. Fibrinógeno aumentó en (B)(288,83±6,8) respecto a (A)(203,33±6,8)(p<0,001), los grupos (C)(196±7,45), (D)(242±7,45) y (E)(104,33±6,8) evidenciaron una regresión significativa de hiperfibrinogenemia(p<0,001). Los niveles de NO disminuyeron en (B)(14,76±1,86) comparado con (A)(27,09±1,95)(p<0,001), su concentración se normalizó en los grupos (C)(25,48±2,06), (D)(22,2±2,33) y (E)(31,25±2,18)(p<0,001). SOD aumentó en (B)(178,64±10,23), (D)(195,71±12,82) y (E)(222,17±15,17)(p<0,001) contrastado con (A)(134,5±10,73)(p<0,001), sin embargo en (C)(145,71±12,82) evidenció disminución significativa respecto a (B)(p<0,001). MO hepática en (B) evidencio congestión centrolobulillar y leve congestión sinusoidales con presencia de hepatocitos binucleados y fenómenos de vacuolización. Los grupos (C), (D) y (E) demostraron regresión de las lesiones descriptas en (B). Nuestros resultados indicaron un estado prooxidativo e inflamatorio con repercusión hepática en (B).Atorvastatina normalizando los biomarcadores analizados y retrogradando las lesiones hepáticas. Metformina logra una reversión de inflamación y EO, con restitución del tejido hepático al evidenciar ausencia de lesiones celulares e inflamatorias. La combinación farmacológica demostró eficacia superior que la monoterapia, actuando cada fármaco en sus blancos biológicos logrando una mayor efectividad en la normalización de las variables bioquímicas y en la regresión de lesiones histológicas. La evidencia actual sobre MAFLD demuestra que ante un mecanismo etiopatogénico complejo es necesario enfoques terapéuticos con múltiples objetivos, la implementación de estos fármacos en lugar de esperar un fármaco ideal que contemple todas las vías moleculares alteradas. . Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2021-10-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion texto texto texto https://revistas.unc.edu.ar/index.php/med/article/view/35106 Revista de la Facultad de Ciencias Médicas de Córdoba.; Vol. 78 No. Suplemento (2021): Suplemento JIC XXII Revista de la Facultad de Ciencias Médicas de Córdoba; Vol. 78 Núm. Suplemento (2021): Suplemento JIC XXII Revista da Faculdade de Ciências Médicas de Córdoba; v. 78 n. Suplemento (2021): Suplemento JIC XXII 1853-0605 0014-6722 http://creativecommons.org/licenses/by-nc/4.0 |