Abstract
Inflammation and hyperlipidemia play an essential role in the pathophysiology of endothelial dysfunction as well as atherosclerotic plaque formation, progression and rupture. Colchicine has direct anti-inflammatory effects by inhibiting multiple inflammatory signaling pathways. The purpose of our study was to evaluate colchicine activity in an animal model of hyperlipidemia induced by diet. A total of 24 male rats (wild type, WT) were divided into three groups: group one fed with a basic diet (BD) (WT + BD, n = 8), group two fed with a high-fat diet (HFD) (WT + HFD, n = 8)), and group three which received HFD plus drug treatment (colchicine, 0.5 mg/kg, i.p., daily administration). Total cholesterol, LDL-, HDL-cholesterol and triglycerides were determined. In addition, plasma transaminases, inflammation of oxidative stress markers, were measured. Tissue samples were evaluated using hematoxylin-eosin and red oil stain. At the end of the study, rats presented increased serum lipid levels, high oxidative stress and pro-inflammatory markers. The aortic histopathological section revealed that HFD induced signs of endothelial dysfunction. Colchicine treatment significantly resolved and normalized these alterations. Moreover, colchicine did not influence NAFLD activity score but significantly increased ALT and AST levels, suggesting that colchicine amplified the hepatocellular injury produced by the diet. Colchicine reduces plasma lipid levels, oxidative stress and inflammation markers and leads to more favorable histopathologic vascular and cardiac results. However, the adverse effects of colchicine could represent an obstacle to its safe use.
Highlights
Cardiovascular diseases (CVD) are one of the major causes of death in the Western world, representing the most important mortality factor worldwide, leading to around20 million deaths annually, accounting for 31.5% of all deaths [1]
Atherosclerosis was historically defined by the retention of lipids in the arterial wall [7,8,9]; newer research has changed this paradigm revealing that inflammation is a crucial factor in vascular pre-atherosclerotic modifications caused by dyslipidemia [10,11,12]
Hyperlipidemia can increase the production of free radicals from the mitochondrial electron transport chain or nicotinamide adenine dinucleotide phosphate (NADPH) activation oxidase [17]
Summary
Cardiovascular diseases (CVD) are one of the major causes of death in the Western world, representing the most important mortality factor worldwide, leading to around20 million deaths annually, accounting for 31.5% of all deaths [1]. Cardiovascular diseases (CVD) are one of the major causes of death in the Western world, representing the most important mortality factor worldwide, leading to around. Antioxidants 2022, 11, 230 heart disease and cerebrovascular disease, accounting for nearly 2.6 million deaths globally each year [1]. Dyslipidemia can result in structural and functional vascular modifications, leading to cardiac consequences such as coronary atherosclerosis and ischemic heart disease (IHD) [4,5,6]. Interleukine-1β (IL-1β), interleukine-6 (IL6), tumor necrosis factor-α (TNF-α) and CRP could represent new therapeutic targets for anti-inflammatory treatment in endothelial dysfunction for reducing the risk of atherosclerotic cardiovascular disease (ASCVD) [15,16].
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