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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| Autores principales: | , , , , , |
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| Formato: | Artículo revista |
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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 |
| Aporte de: |
| Sumario: | 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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