Pharmacological Action of Atorvastatin and Metformin on Non-alcoholic
Fatty Liver Disease on an Experimental Model of Metabolic Syndrome
Authors: Augusto Castillo Tomas , de la Paz Scribano Parada María , Rossi Micaela Milagros , Signorini Franco , Fonseca Ismael , del Carmen Baez María 
Published: February 2023

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).

background:
Non-alcoholic fatty liver disease (NAFLD) is the world&#039;s most frequent cause of chronic liver disease. It is known 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.

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 0.035mg/day/rat, metformin 1.78mg/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.

method:
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 0.035mg/day/rat, metformin 1.78mg/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 the liver were analyzed by light microscopy. Comparisons of all possible combinations of pairs of means were made by multivariate ANOVA and Hotelling (as a post hoc test). A significance level of p&amp;lt;0.05 was established for all cases.

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.