Effects of Colchicine in a Rat Model of Diet-Induced Hyperlipidemia

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.

RETRACTED: Histological, ultrastructural and immunohistochemical studies on the ameliorative role of Cinnamon zeylanicum against high cholesterol diet-induced hypercholesterolemia in the kidney of adult male albino rats

“…Excess cholesterol caused several diseases including atherosclerosis ( Hall, 2016 ), infertility ( Mahdavi et al., 2021 ) and toxicity in different organs as the liver ( Yu et al., 2021 ), thyroid gland ( Rasekh et al., 2021 ) and kidney ( Kaur et al., 2021 ). Zălar et al. (2022) reported that rats-fed a high-fat diet for 4 weeks showed an increase in oxidative stress, pro-inflammatory markers as well as induced signs of endothelial dysfunction in aorta sections.…”

Amino Acid Conjugates of 2-Mercaptobenzimidazole Ameliorates High-Fat Diet-Induced Hyperlipidemia in Rats via Attenuation of HMGCR, APOB, and PCSK9

“…4J and 4K Attenuated HFD-Induced AST and ALT Levels. HFD is known to alter liver functions and can cause fatty liver disease; 27 we therefore measured aspartate aminotransferase (AST) and alanine transaminase (ALT) levels. As expected, the disease group and SIM-treated group showed prominent increase in AST and ALT levels indicating liver dysfunction.…”

Association between Clinical Use of Colchicine and Risk of Type 2 Diabetes Mellitus among Gouty Patients: A Nationwide Cohort Study

“…Animal studies showed that colchicine reduces the inflammatory response and enhances the antioxidant capacity in rats fed with a high-fat diet [ 31 ]. In addition, colchicine treatment induced a protective effect on oxidative stress, the antioxidant redox system, and Ca2 released in serum and polymorphonuclear leucocytes of familial Mediterranean fever patients in remission that are characterized by oxidative stress [ 32 ]. Thus, colchicine treatment could induce a protective effect on diabetic risk via a regulatory effect on inflammatory processes and oxidative stress.…”