Pharmacological Action of Atorvastatin and Metformin on Non-alcoholic Fatty Liver Disease on an Experimental Model of Metabolic Syndrome.

Q2 Medicine

Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry Pub Date : 2023-01-01 DOI:10.2174/1871523022666230223090714

Castillo Tomas Augusto, María de la Paz Scribano Parada, Micaela Milagros Rossi, Franco Signorini, Ismael Fonseca, María del Carmen Baez

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引用次数: 0

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in the world. It is known that there is a pathogenic relation between liver damage and the inflammatory and oxidative environment present in Metabolic Syndrome (MS).

Objective: To study the pharmacological action of atorvastatin and metformin in an experimental model of MS.

Methods: We used 40 male rats (Wistar) divided into the following groups: Control (A) (n=8), induced MS (B) (n=8), MS + atorvastatin treatment (C)(n=8), MS + metformin treatment (D) (n=8) and MS + combined treatment (E) (n=8). MS was induced by administering 10% fructose in drinking water for 45 days. Atorvastatin 0.035 mg/day/rat, metformin 1.78 mg/day/rat, and a combination of both drugs were administered for 45 days. Metabolic, oxidative (nitric oxide, myeloperoxidase and superoxide dismutase) and inflammatory (fibrinogen) parameters were determined. Histological sections of liver were analyzed by light microscopy.

Results: The glycemia, lipid profile and TG/HDL-C index were altered in MS group. After pharmacological treatment, metabolic parameters improve significantly in all treated groups. Inflammatory and oxidative stress biomarkers increase in MS. Treated groups showed an increase in NO bioavailability, no difference in MPO activity and an increase in fibrinogen. Atorvastatin showed a decrease in SOD while Metformin and combination treatment showed an increase in SOD compared to MS. In MS, we observed histological lesions consistent with NAFLD. However, after a combined treatment, we observed total regression of these lesions.

Conclusion: Our results showed that there is an important synergy between atorvastatin and metformin in improving liver involvement in MS.

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阿托伐他汀和二甲双胍对代谢综合征实验模型非酒精性脂肪肝的药理作用

背景:非酒精性脂肪性肝病(NAFLD)是世界上最常见的慢性肝病。已知代谢综合征(MS)中肝脏损伤与炎症和氧化环境之间存在致病关系。目的:研究阿托伐他汀和二甲双胍对MS实验模型的药理作用。方法:选取雄性Wistar大鼠40只，分为对照组(A) (n=8)、诱导MS (B) (n=8)、MS +阿托伐他汀治疗组(C)(n=8)、MS +二甲双胍治疗组(D) (n=8)和MS +联合治疗组(E) (n=8)。用10%果糖灌胃45 d诱导多发性硬化症。阿托伐他汀0.035 mg/天/只，二甲双胍1.78 mg/天/只，联合用药45天。测定代谢、氧化(一氧化氮、髓过氧化物酶和超氧化物歧化酶)和炎症(纤维蛋白原)参数。光镜下分析肝脏组织切片。结果:MS组血糖、血脂及TG/HDL-C指数发生改变。药物治疗后，各治疗组代谢指标均有明显改善。ms治疗组炎症和氧化应激生物标志物增加，NO生物利用度增加，MPO活性和纤维蛋白原增加无差异。与MS相比，阿托伐他汀组SOD降低，而二甲双胍和联合治疗组SOD升高。在MS中，我们观察到与NAFLD一致的组织学病变。然而，在联合治疗后，我们观察到这些病变完全消退。结论:我们的研究结果表明，阿托伐他汀和二甲双胍在改善多发性硬化症肝脏受累方面有重要的协同作用。

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来源期刊

Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

3.30

自引率

0.00%

发文量

期刊介绍： Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new anti-inflammatory & anti-allergy agents. Publishing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.