Synergistic effects of atorvastatin and rosiglitazone on endothelium protection in rats with dyslipidemia

Autor: Zhi-Peng Zou, Wen-Ju Yan, Bei Sun, Wei Li Zhang
Rok vydání: 2014
Předmět:
Male
medicine.medical_specialty
Endothelium
Clinical chemistry
Atorvastatin
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Drug Evaluation
Preclinical
Pharmacology
Rats
Sprague-Dawley
Rosiglitazone
chemistry.chemical_compound
Endocrinology
Internal medicine
medicine
Animals
Pyrroles
Endothelial dysfunction
Dyslipidemias
Biochemistry
medical
Inflammation
medicine.diagnostic_test
business.industry
Anticholesteremic Agents
Myocardium
Research
Biochemistry (medical)
nutritional and metabolic diseases
Drug Synergism
medicine.disease
Atherosclerosis
Oxidative Stress
medicine.anatomical_structure
chemistry
Dyslipidemia
Cytoprotection
Heptanoic Acids
lipids (amino acids
peptides
and proteins)
Thiazolidinediones
Endothelium
Vascular
Asymmetric dimethylarginine
Lipid profile
business
medicine.drug
Zdroj: Lipids in Health and Disease
ISSN: 1476-511X
Popis: Background: Endothelial dysfunction is implicated in the initiation and progression of atherosclerosis. Whether atorvastatin combined with rosiglitazone has synergistic effects on endothelial function improvement in the setting of dyslipidemia is unknown. Methods: Dyslipidemia rat model was produced with high-fat and high-cholesterol diet administration. Thereafter, atorvastatin, rosiglitazone or atorvastatin combined with rosiglitazone were prescribed for 2 weeks. At baseline, 6 weeks of dyslipidemia model production, and 2 weeks of medical intervention, fasting blood was drawn for parameters of interest evaluation. At the end, myocardium was used for 15-deoxy-delta-12,14-PGJ2 (15-d-PGJ2) assessment. Results: Initially, there was no significant difference of parameters between sham and dyslipidemia groups. With 6 weeks’ high-fat and high-cholesterol diet administration, as compared to sham group, serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) were significantly increased. Additionally, nitric oxide (NO) production was reduced and serum levels of malondialdehyde (MDA), C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA) were profoundly elevated in dyslipidemia group. After 2 weeks’ medical intervention, lipid profile was slightly improved in atorvastatin and combined groups as compared to control group. Nevertheless, in comparison to control group, NO production was profoundly increased and serum levels of MDA, CRP and ADMA were significantly decreased with atorvastatin or rosiglitazone therapy. 15-d-PGJ2 expression of myocardium was also significantly elevated with atorvastatin or rosiglitazone treatment. Notably, these effects were further enhanced with combined therapy, suggesting that atorvastatin and rosiglitazone had synergistic effects on endothelial protection, and inflammation and oxidation amelioration. Conclusion: Atorvastatin and rosiglitazone therapy had synergistic effects on endothelium protection as well as amelioration of oxidative stress and inflammatory reaction in rats with dyslipidemia.
Databáze: OpenAIRE
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