Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers
Metabolic syndrome (MS) is recognized as a clinical-pathological entity, where central obesity and insulin resistance/compensatory hyperinsulinemia are the pathophysiological triggers of this disease. It has been determined that in MS a state of low-grade systemic inflammation is generated. It...
| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
| Lenguaje: | Español |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2019
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/25704 |
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I10-R327-article-25704 |
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ojs |
| institution |
Universidad Nacional de Córdoba |
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I-10 |
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R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| language |
Español |
| format |
Artículo revista |
| topic |
metabolic syndrome inflamation oxidative stress atorvastatin metformin síndrome metabólico inflamación estrés oxidativo atorvastatina metformina |
| spellingShingle |
metabolic syndrome inflamation oxidative stress atorvastatin metformin síndrome metabólico inflamación estrés oxidativo atorvastatina metformina Castillo, TA Scribano Parada, MP Tarán, M Balceda, A Rossi, MM Blencio, S Moya, M Baez, MC Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| topic_facet |
metabolic syndrome inflamation oxidative stress atorvastatin metformin síndrome metabólico inflamación estrés oxidativo atorvastatina metformina |
| author |
Castillo, TA Scribano Parada, MP Tarán, M Balceda, A Rossi, MM Blencio, S Moya, M Baez, MC |
| author_facet |
Castillo, TA Scribano Parada, MP Tarán, M Balceda, A Rossi, MM Blencio, S Moya, M Baez, MC |
| author_sort |
Castillo, TA |
| title |
Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| title_short |
Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| title_full |
Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| title_fullStr |
Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| title_full_unstemmed |
Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| title_sort |
pharmacological analysis of metabolic syndrome appraised by oxidative stress markers |
| description |
Metabolic syndrome (MS) is recognized as a clinical-pathological entity, where central obesity and insulin resistance/compensatory hyperinsulinemia are the pathophysiological triggers of this disease. It has been determined that in MS a state of low-grade systemic inflammation is generated. It is characterized by the abnormal production of proinflammatory cytokines associated with an oxidative stress (OS) state secondary to the inflammatory process that leads to a systemic redox alteration affecting different targets. There are no studies of drugs that act on this state, therefore it was decided to evaluate the possible therapeutic responses of atorvastatin and metformin, first-line drugs used in states of hyperlipidemia and hyperglycemia respectively. Objective: to study the pharmacological action of atorvastatin and metformin, and its effects on OS markers in experimental MS.
32 adult Wistar male rats of average weight 280±20 g were used, divided into (A) Control (n=8), (B) MS (n=8), (C) MS+atorvastatin (n=8), (D) MS+metformin (n=8). MS was induced with 10% fructose in drinking water for 6 weeks, then 0.035mg/day atorvastatin and 1.78mg/day metformin was administered for 45 days with noxa persisting. Serum OS markers: Nitric oxide(NO)(μM), superoxide dismutase (SOD) (U/ml) quantified by spectrophotometry and myeloperoxidase (MPO)(U/mg) quantified by ELISA. Statistics: Bonferroni and Hotelling as post hoc test, significance p<0.05.
NO significantly decreased in group (B)(14.76±4.43) compared to (A)(26.01±2.78), and a significant increase was demonstrated in (C)(25.08±3.06) and in (D)(22.20±3.26) with respect to (B)(p<0.001). When analyzing the activity of SOD, a significant increase was observed in (B)(178.64±23.70) respect to (A)(135±12.25), and a significant decrease in (C)(145.71±25.41) in relation to (B)(p<0.01); no differences were found in (A) vs (C). MPO presented a similar behavior in (B)(181.30±12.06) when compared to (A)(116.07±10.32); (D)(113.07±14.90) on the other hand, evidenced a significant decrease when compared to (B)(p<0.01).
In SM a state of EO is evidenced by demonstrating an increase in SOD and MPO and a decrease in the bioavailability of NO in relation to control. Atorvastatin showed a regression of the prooxidative state evidenced by a normalization in the levels of NO and SOD, probably related to its pleiotropic effects. Regarding the group with metformin, there was restitution in the bioavailability of NO and decrease in MPO, this could be related to an anti-inflammatory action of the drug.
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| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2019 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/25704 |
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I10-R327-article-257042024-08-27T18:26:05Z Pharmacological analysis of metabolic syndrome appraised by oxidative stress markers Análisis farmacológico de síndrome metabólico valorado por marcadores de estrés oxidativo. Castillo, TA Scribano Parada, MP Tarán, M Balceda, A Rossi, MM Blencio, S Moya, M Baez, MC metabolic syndrome inflamation oxidative stress atorvastatin metformin síndrome metabólico inflamación estrés oxidativo atorvastatina metformina Metabolic syndrome (MS) is recognized as a clinical-pathological entity, where central obesity and insulin resistance/compensatory hyperinsulinemia are the pathophysiological triggers of this disease. It has been determined that in MS a state of low-grade systemic inflammation is generated. It is characterized by the abnormal production of proinflammatory cytokines associated with an oxidative stress (OS) state secondary to the inflammatory process that leads to a systemic redox alteration affecting different targets. There are no studies of drugs that act on this state, therefore it was decided to evaluate the possible therapeutic responses of atorvastatin and metformin, first-line drugs used in states of hyperlipidemia and hyperglycemia respectively. Objective: to study the pharmacological action of atorvastatin and metformin, and its effects on OS markers in experimental MS. 32 adult Wistar male rats of average weight 280±20 g were used, divided into (A) Control (n=8), (B) MS (n=8), (C) MS+atorvastatin (n=8), (D) MS+metformin (n=8). MS was induced with 10% fructose in drinking water for 6 weeks, then 0.035mg/day atorvastatin and 1.78mg/day metformin was administered for 45 days with noxa persisting. Serum OS markers: Nitric oxide(NO)(μM), superoxide dismutase (SOD) (U/ml) quantified by spectrophotometry and myeloperoxidase (MPO)(U/mg) quantified by ELISA. Statistics: Bonferroni and Hotelling as post hoc test, significance p<0.05. NO significantly decreased in group (B)(14.76±4.43) compared to (A)(26.01±2.78), and a significant increase was demonstrated in (C)(25.08±3.06) and in (D)(22.20±3.26) with respect to (B)(p<0.001). When analyzing the activity of SOD, a significant increase was observed in (B)(178.64±23.70) respect to (A)(135±12.25), and a significant decrease in (C)(145.71±25.41) in relation to (B)(p<0.01); no differences were found in (A) vs (C). MPO presented a similar behavior in (B)(181.30±12.06) when compared to (A)(116.07±10.32); (D)(113.07±14.90) on the other hand, evidenced a significant decrease when compared to (B)(p<0.01). In SM a state of EO is evidenced by demonstrating an increase in SOD and MPO and a decrease in the bioavailability of NO in relation to control. Atorvastatin showed a regression of the prooxidative state evidenced by a normalization in the levels of NO and SOD, probably related to its pleiotropic effects. Regarding the group with metformin, there was restitution in the bioavailability of NO and decrease in MPO, this could be related to an anti-inflammatory action of the drug. Se reconoce al síndrome metabólico (SM) como una entidad clínico-patológica, donde la obesidad central y la insulinorresistencia/hiperinsulinemia compensadora son los disparadores fisiopatológicos de esta enfermedad. Se ha demostrado que en SM se genera un estado de inflamación sistémica de bajo grado, caracterizado por la producción anormal de citoquinas proinflamatorias asociado a un estado de estrés oxidativo (EO) secundario al proceso inflamatorio que conlleva a una alteración redox sistémica repercutiendo en diferentes órganos blanco. No existen estudios de fármacos que actúen sobre este estado, por lo tanto se decidió evaluar en este trabajo las posibles respuestas terapéuticas de atorvastatina y metformina, drogas de primera línea usadas en estados de hiperlipidemia e hiperglucemia respectivamente. Objetivo: Estudiar, en SM experimental, la acción farmacológica de atorvastatina y metformina, y sus efectos sobre marcadores de EO. Se utilizaron 32 ratas macho Wistar adultas de peso promedio 280 ± 20 g, dividida en: (A) Control (n=8), (B) SM (n=8), (C) SM+atorvastatina (n=8), (D) SM+metformina (n=8). SM fue inducido con fructosa 10% en agua de bebida durante 6 semanas, luego se administró 0,035mg/día/rata de atorvastatina y 1,78mg/día/rata de metformina durante 45 días persistiendo la noxa. Marcadores de EO séricos: Óxido nítrico (NO)(μM), superóxido dismutasa (SOD)(U/ml) cuantificados por espectrofotometría y mieloperoxidasa (MPO)(U/mg) cuantificada por ELISA. Estadística: Bonferroni y Hotelling como test post hoc, significación p<0.05. NO evidenció en el grupo (B)(14,76±4,43) una disminución significativa comparado con (A)(26,01±2,78), y se demostró incremento significativo en (C)(25,08±3,06) y en (D)(22,20±3,26) con respecto a (B)(p<0,001). Al analizar la actividad de SOD, se observó en (B)(178,64±23,70) un aumento significativo respecto al grupo (A)(135±12,25), y en (C)(145,71±25,41) disminución significativa con relación a (B)(p<0,01), sin diferencia en (A) vs (C). Similar comportamiento presentó MPO en (B)(181,30±12,06) comparado con (A)(116,07±10,32), por otra parte, en (D)(113,07±14,90) se evidenció disminución significativa en comparación con (B)(p<0,01). En SM se evidencia un estado de EO al demostrarse incremento de SOD y MPO y con disminución en la biodisponibilidad de NO en relación al control. Atorvastatina mostró una regresión del estado prooxidativo evidenciado por una normalización en los niveles de NO y SOD, relacionados probablemente a sus efectos pleiotrópicos. Respecto al grupo con metformina, existió restitución en la biodisponibilidad de NO y disminución de MPO, esto podria estar relacionado con una acción antiinflamatoria del fármaco. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2019-10-10 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/25704 Revista de la Facultad de Ciencias Médicas de Córdoba.; 2019: Suplemento JIC XX Revista de la Facultad de Ciencias Médicas de Córdoba; 2019: Suplemento JIC XX Revista da Faculdade de Ciências Médicas de Córdoba; 2019: Suplemento JIC XX 1853-0605 0014-6722 10.31053/1853.0605.v76.nSuplemento spa https://revistas.unc.edu.ar/index.php/med/article/view/25704/27400 Derechos de autor 2019 Universidad Nacional de Córdoba https://creativecommons.org/licenses/by-nc/4.0 |