Rosuvastatin-loaded glycerosomes protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats by modulating lipid profiles, oxidative stress, and specific signaling pathways.
Does rosuvastatin-loaded glycerosomes improve lipid profiles and atheroprotective pathways in dyslipidemic rats?
Rosuvastatin-loaded glycerosomes protect against NAFLD and atherosclerosis progression in dyslipidemic rats by modulating lipid profiles, oxidative stress, and specific hepatic and aortic signaling pathways.
Abstract Dyslipidemia is a major risk factor for the development of NAFLD, atherosclerosis and cardiovascular diseases. Rosuvastatin (ROS) is a lipid-lowering drug that protects against the development of NAFLD and atherosclerosis. However, the mechanism of this protection remains obscure. Therefore, the current study aims to explore the mechanism by which ROS-loaded glycerosomes (ROS-GLY) protect against NAFLD and atherosclerosis. Hence, for this purpose, hepatic lncRNA-H19/miR-130a/PPAR-γ and aortic PPAR-γ/LXRα/ABCA1 signaling pathways were assessed. In addition, these target pathways were predicted using molecular docking analysis. Thirty-five male Sprague Dawley rats were separated into control, dyslipidemic (poloxamer 407 (P 407)), P 407+ROS-GLY, P 407+NC, and P 407+ROS-GLY+NC groups. ROS-GLY improved lipid profile, hepatic MDA, SOD, catalase and total antioxidant capacity (TAC) in compared to P 407 group. In the dyslipidemic group, ROS-GLY downregulated hepatic lncRNA-H19 expression which leads to an upregulate of the miR-130a level and subsequent reduction of the PPAR-γ level. Consequently, the hepatic expression level of lipogenic genes such as, ACC-1, FASN and SCD-1 was significantly downregulated in the ROS-GLY group than the dyslipidemic one. Aortic PPAR-γ/LXRα/ABCA1 signaling pathway was significantly upregulated in the ROS-GLY group compared to the dyslipidemic group. Furthermore, ROS-GLY modulated IL-6 and IL-10 immunoprotein expression in hepatic and aortic tissues. Interestingly, ROS showed a substantial binding affinity with PPAR-γ, LXR-α, and FASN, according to a molecular docking study. The current study indicated that ROS-GLY protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats via modulation of lipid profile, oxidative stress, pro-/anti-inflammatory cytokines, hepatic lncRNA-H19/miR-130a/PPAR-γ, and aortic PPAR-γ/LXRα/ABCA1 signaling pathways.
Mansour et al. (Thu,) conducted a other in Dyslipidemia (n=35). Rosuvastatin-loaded glycerosomes (ROS-GLY) vs. Poloxamer 407 (P 407) induced dyslipidemia was evaluated. Rosuvastatin-loaded glycerosomes protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats by modulating lipid profiles, oxidative stress, and specific signaling pathways.
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