Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress
Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of...
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MDPI AG
2022-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/3/716 |
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| author | Evelyn Nunes Goulart da Silva Pereira Beatriz Peres de Araujo Karine Lino Rodrigues Raquel Rangel Silvares Carolina Souza Machado Martins Edgar Eduardo Ilaquita Flores Caroline Fernandes-Santos Anissa Daliry |
| author_facet | Evelyn Nunes Goulart da Silva Pereira Beatriz Peres de Araujo Karine Lino Rodrigues Raquel Rangel Silvares Carolina Souza Machado Martins Edgar Eduardo Ilaquita Flores Caroline Fernandes-Santos Anissa Daliry |
| author_sort | Evelyn Nunes Goulart da Silva Pereira |
| collection | DOAJ |
| description | Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters. |
| first_indexed | 2024-03-09T23:20:40Z |
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| id | doaj.art-946b6c5a2fe246e7a7d84dfe1884922d |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T23:20:40Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-946b6c5a2fe246e7a7d84dfe1884922d2023-11-23T17:28:25ZengMDPI AGNutrients2072-66432022-02-0114371610.3390/nu14030716Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE StressEvelyn Nunes Goulart da Silva Pereira0Beatriz Peres de Araujo1Karine Lino Rodrigues2Raquel Rangel Silvares3Carolina Souza Machado Martins4Edgar Eduardo Ilaquita Flores5Caroline Fernandes-Santos6Anissa Daliry7Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilLaboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Pavilhão Ozório de Almeida Av. Brasil, 4365 (Room 14), Manguinhos, Rio de Janeiro 21040-900, RJ, BrazilIncreased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters.https://www.mdpi.com/2072-6643/14/3/716nonalcoholic fatty liver diseasesimvastatinmicrocirculationliveradipose tissue |
| spellingShingle | Evelyn Nunes Goulart da Silva Pereira Beatriz Peres de Araujo Karine Lino Rodrigues Raquel Rangel Silvares Carolina Souza Machado Martins Edgar Eduardo Ilaquita Flores Caroline Fernandes-Santos Anissa Daliry Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress Nutrients nonalcoholic fatty liver disease simvastatin microcirculation liver adipose tissue |
| title | Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress |
| title_full | Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress |
| title_fullStr | Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress |
| title_full_unstemmed | Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress |
| title_short | Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress |
| title_sort | simvastatin improves microcirculatory function in nonalcoholic fatty liver disease and downregulates oxidative and ale rage stress |
| topic | nonalcoholic fatty liver disease simvastatin microcirculation liver adipose tissue |
| url | https://www.mdpi.com/2072-6643/14/3/716 |
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