RESUMO
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.
RESUMO
BACKGROUND: Hyperlipidemia and inflammation are critical components in the pathophysiology of endothelial disorder, which can lead to vascular complications. Our study aimed to evaluate the effects of immunomodulatory therapy (methotrexate and infliximab) in a diet-induced hyperlipidemia rat model. METHODS: Sprague-Dawley (wild type (WT), male, n = 32) rats were divided into four groups: one group fed with standard diet (SD), one group fed with high lipid diet (HLD), and two groups that received HLD and drug treatment (methotrexate (Mtx) or infliximab (Ifx)). In order to evaluate if modifications to the endothelial cells may influence the risk of vascular complications following hyperlipidemia or treatment reactivity, each group was doubled by a rats group that overexpressed beta-3 receptors on the endothelial cells (transgenic (TG-beta 3), male, n = 32). Serum lipid profile, liver enzymes, oxidative stress, and inflammation markers were determined. Histopathologic analysis of the liver and aorta was performed. RESULTS: After 9 weeks of HLD, rats exhibited significant pathologic serum lipid profiles, elevated oxidative stress, and pro-inflammatory markers. Additionally, the aortic histopathological analysis revealed aorta media-intima thickening (p < 0.05) in the transgenic group. Methotrexate and infliximab significantly decreased inflammation and oxidative stress parameters, but presented opposing effects on lipid profiles (methotrexate decreased, whereas infliximab increased the atherosclerosis index). Drug treatment decreased the aorta media-intima thickness (p < 0.05) only in transgenic rats. CONCLUSIONS: HLD was associated with hyperlipidemia, inflammation and oxidative stress. The overexpression of beta-3 receptors on endothelial cells increased aortic thickening in response to the HLD. Methotrexate and infliximab reduced oxidative stress and inflammation in all groups, but led to favorable histopathologic vascular results only in the transgenic groups.
RESUMO
BACKGROUND: The updated model for the mechanism of gastric carcinogenesis demonstrates that Helicobacter pylori (H. pylori) is a risk factor in every step of the process. The expression of certain gastric mucins is altered by H. pylori infection in adult patients. The aim of our research was to assess the impact of H. pylori infection on the expression of secretory mucins in the pediatric antral mucosa. METHODS: Slides were stained with monoclonal antibodies for MUC5AC, MUC6 and MUC2, digitalized and scored using both a semiquantitative and a quantitative approach. RESULTS: The expression of MUC5AC was significantly lower in infected children. Also, MUC2 expression was more pronounced in infected children. MUC6 expression did not differentiate between infected and noninfected children. Additionally, the presence of chronic inflammation significantly altered the expression of MUC6 and MUC2. The expression of MUC6 was significantly higher in patients with gastric atrophy. CONCLUSION: The minor differences in mucin expression at distinct ages might stem from different H. pylori exposure periods. Further research is needed to determine the particular patterns of expression according to age and to evaluate the effects of the interaction between H. pylori and mucins in the progression of the gastric carcinogenesis cascade.
