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

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.

Inflammatory and Oxidative Stress Markers as Indicator of Atherogenesis in Rats: Antioxidants as Preventive Pharmacological Methods.

OBJECTIVE: The oxidative process in atherogenesis generated by proinflammatory induction and response to antioxidants vitamins in an experimental model were analyzed. METHODS: Male rats were used: (A)Control, (B)Control+vitamin E plus C, (C)Hyperfibrinogenemia and (D)Hyperfibrinogenemia+vitamins E plus C. Hyperfibrinogenemia induced by daily injection of adrenaline (0.1mg/day/rat) for 120 days. TREATMENT: 3.42 mg/kg of vitamin E plus 2.14 mg/kg of vitamin C, fifteen days after induction. Vascular histology analyzed by optical microscopy. Fibrinogen, nitrites and superoxide dismutase analyzed by spectrophotometry. STATISTICS: MANOVA, Hotelling test for post testing, significance level p<0.05. RESULTS: (C) group showed higher fibrinogen than (A) and (B)(p<0.001). Compared to (C) group, (D) showed a decrease of fibrinogen (p<0.001). A marked increase in nitrites was found in (C) versus (A), (B) and (D) groups (p<0.001). Superoxide dismutase activity increased in (C) group compared to groups (A) and (B) (p<0.001). In the group (D) an increase of the activity of this enzyme was observed in comparison to groups (C)(p<0.001), (A) and (B) (p<0.0001 in both). The (C) group shown endothelial denudation, thickening of the vascular intima and extracellular matrix enlargement with foam cells(p<0.001). CONCLUSION: These results strongly suggest that vitamins E plus C produce regression of inflammatory and oxidative stress processes in this experimental model.