Evaluation of Oxidative Stress Biomarkers, Pro-Inflammatory Cytokines, and Histological Changes in Experimental Hypertension, Dyslipidemia, and Type 1 Diabetes Mellitus

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1438
• Main Authors: Boarescu, Paul-Mihai, Boarescu, Ioana, Pop, Raluca Maria, Roşian, Ştefan Horia, Bocșan, Ioana Corina, Rus, Vasile, Mada, Răzvan Olimpiu, Popa, Iulia Diana, Neagu, Nicholas, Bulboacă, Adriana Elena, Buzoianu, Anca Dana, Bolboacă, Sorana D
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Arginine; Arteries; Atherosclerosis; Biomarkers; Biomarkers - metabolism; Blood pressure; Blood vessels; Body weight; Cardiomyopathy; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Coronary vessels; Cytokines; Cytokines - metabolism; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - metabolism; Diet, High-Fat - adverse effects; Disease Models, Animal; Dyslipidemia; Dyslipidemias - chemically induced; Dyslipidemias - metabolism; Evaluation; Glucose; High cholesterol diet; High density lipoprotein; Hypertension; Hypertension - chemically induced; Hypertension - metabolism; IL-1β; Inflammation; Interleukin 6; Lipids; Lipoproteins; Male; Malondialdehyde; Malondialdehyde - metabolism; Metabolic disorders; NG-Nitroarginine methyl ester; NG-Nitroarginine Methyl Ester - adverse effects; Nitric Oxide - metabolism; Oral administration; Oxidative Stress; Pathogenesis; Rats; Risk analysis; Risk factors; Smooth muscle; Streptozocin; Streptozocin - adverse effects; Sulfhydryl Compounds; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; type 1 diabetes mellitus; Veins & arteries
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031438

The present study aims to compare the oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes induced by three cardiovascular risk factors, namely, hypertension, dyslipidemia, and type 1 diabetes mellitus. Hypertension was induced with 40 mg/kg body weight (b.w.) of N omega-nitro-L-arginine-methyl (L-NAME) administered orally. Dyslipidemia was induced by the administration of a diet with a high cholesterol (2%) content. Diabetes mellitus was induced by intraperitoneal administration of a single dose of streptozocin (65 mg/kg). Malondialdehyde (MDA) and total oxidative status (TOS) are increased by all three cardiovascular risk factors (up to 207%). The indirect assessment of NO synthesis (NOx) is observed to be reduced after L-NAME administration (43%), and dyslipidemia induction (16%), while type 1 diabetes mellitus is associated with the highest levels of NOx (increased 112%). Hypertension, dyslipidemia, and type 1 diabetes reduced the total antioxidative capacity (TAC) and total thiol (SH) levels (up to 57%). The values of evaluated pro-inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), assessed from the ascending aorta were elevated by all three cardiovascular risk factors, with the highest levels induced by type 1 diabetes mellitus (up to 259%). The histopathological examination of the ascending and descending aorta revealed reversible pro-atherogenic changes consisting of the accumulation of lipid droplets in the subendothelial connective tissue on rats with hypertension and dyslipidemia. Irreversible pro-atherogenic changes consisting of a reduction of the specific elasticity of the arteries were observed in rats with type 1 diabetes mellitus. Type 1 diabetes mellitus demonstrates an alteration of the oxidative stress parameters, the elevation of tissue levels of the pro-inflammatory cytokines and causing irreversible pro-atherogenic changes on the aortic wall.