Stanozolol promotes lipid deposition in the aorta through an imbalance in inflammatory cytokines and oxidative status in LDLr knockout mice fed a normal diet

• Published in: Basic & clinical pharmacology & toxicology 2019-04, Vol.124 (4), p.360-369
• Main Authors: Andrade, Tadeu Uggere, Haguihara, Silvia Cruz Goes Coutinho, Falsoni, Raiana Maria Prucoli, Silva, Cristiane Lyrio, Dubois Filho, Dionísio Gonzaga, Souza Andrade Moraes, Flávia, Nascimento, Andrews Marques, Brasil, Girlandia Alexandre, Lima, Ewelyne Miranda
• Format: Article
• Language: English
• Subjects: Anabolic Agents - toxicity; Animals; Aorta; Aorta - drug effects; Aorta - pathology; Arteriosclerosis; Atherosclerosis; Atherosclerosis - chemically induced; Atherosclerosis - pathology; Cholesterol; Coronary vessels; Cytokines; Cytokines - metabolism; Deposition; Diet; Disease Models, Animal; Disease Progression; High density lipoprotein; IL‐10; Inflammation; Inflammation - chemically induced; Inflammation - pathology; Inflammation Mediators - metabolism; Interleukins; LDLr; Lipid Metabolism - drug effects; Lipid peroxidation; Lipids; Lipoproteins, LDL - metabolism; Liver; Low density lipoprotein receptors; Male; Mice; Mice, Knockout; Oxidation; Oxidation-Reduction - drug effects; Oxidative stress; Oxidative Stress - drug effects; OxLDL; Peroxidation; Proteins; Receptor density; Receptors; Receptors, LDL - genetics; Stanozolol; Stanozolol - toxicity; Steroids; Thiobarbituric acid; TNF‐α; Triglycerides; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumors
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13143

The aim of the study was to evaluate the effect of an anabolic steroid, stanozolol, in a model of atherosclerosis and to investigate the involvement of the modulation of the inflammatory cytokines and oxidative stress in vascular lipid deposition. Low‐density lipid receptor‐deficient (LDLr−/−) mice were fed a standard chow diet and were each week injected subcutaneously either saline (control C group) or 20 mg/kg stanozolol (S group). After 8 weeks, the levels of cholesterol, oxidized LDL (OxLDL) and cytokines were measured in plasma, lipid deposition in aorta was evaluated by en face analysis, and thiobarbituric acid‐reactive substances and oxidation protein were determined in liver. The S group demonstrated increases in vascular lipid deposition, triglycerides and non‐HDL cholesterol levels. Stanozolol increased tumour necrosis factor alpha (TNF‐α) and decreased interleukin‐10 as well as increased the TNF‐α/IL‐10 ratio. Furthermore, oxidative stress was observed in the S group, as indicated by an increase in the plasma OxLDL, as well as by lipid peroxidation and oxidation of proteins in the liver. Chronic treatment with stanozolol promoted lipid deposition in the LDLr−/− mice that could be attributed to a modification of the circulating cytokine levels and systemic oxidative stress. Our results suggest that the anabolic steroid stanozolol in the absence of functional LDL receptors by increasing systemic inflammation and oxidative stress may increase the risk of development and progression of atherosclerosis.