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

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.

Pharmacological Effects of Methotrexate and Infliximab in a Rats Model of Diet-Induced Dyslipidemia and Beta-3 Overexpression on Endothelial Cells.

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.

Antibiotics in the environment: causes and consequences.

Antibiotics represent one of the main discoveries of the last century that changed the treatment of a large array of infections in a significant way. However, increased consumption has led to an exposure of bacterial communities and ecosystems to a large amount of antibiotic residues. This paper aims to provide a brief overview of the primary drivers associated with antibiotic occurrence in the environment. Furthermore, we attempted to summarize the behavior of antibiotic residues in the environment and the necessity of their detection and quantification. Also, we provide updated scientific and regulatory facts about environmental antibiotic discharge and environmental and human antibiotics risk assessment. We propose that environmental antibiotic contamination should be diminished beginning from regulating the causes of occurrence in the environment (such as antibiotic consumption) and ending with regulating antibiotic discharge and risk assessment. Some important intermediate steps are represented by the detection and quantification of the antibiotics and the characterization of their behavior in the environment, which could come to support future regulatory decisions.

Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients.

(1) Background: Prescribing apixaban for stroke prevention has significantly increased in patients with non-valvular atrial fibrillation (NVAF). The ABCB1 genotype can influence apixaban absorption and bioavailability. The aim of the present study was to assess the factors that influence apixaban's plasma level and to establish if a certain relationship has clinical relevance. (2) Methods: Fifty-three NVAF patients were treated with 5 mg apixaban twice/day (70.0 years, range: 65-77, 60.4% men). Trough and peak plasma concentrations of apixaban were determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS), and ABCB1 genotyping was performed. (3) Results: Apixaban plasma concentrations varied considerably. They were higher in women than in men (311.2 ng/dL vs. 252.2 ng/dL; p = 0.05) and were lower in patients with heart failure (149.4 ng/dL vs. 304.5 ng/dL; p < 0.01). Creatinine clearance was inversely correlated with the apixaban plasma level (Spearman correlation: r = -0.365; p = 0.007 for trough concentrations). No statistically significant differences between the genotypic groups of ABCB1 rs1045642 and ABCB1 rs4148738 were found in the trough or peak apixaban plasma concentrations. (4) Conclusions: Pharmacokinetic parameters are influenced by several clinical factors of which renal function is the major determinant. Plasma concentrations measured in women had higher values than those measured in men, and heart failure was associated with decreased plasma levels of apixaban.

Antioxidant Effects of Walnut (Juglans regia L.) Kernel and Walnut Septum Extract in a D-Galactose-Induced Aging Model and in Naturally Aged Rats.

Antioxidant dietary intervention is considered a potential strategy in delaying age-related dysfunctions. In this study of 56 days, we assessed the antioxidant effects of walnut kernel (WK) and walnut septum extract (WSE) in a D-galactose (D-gal)-induced aging model and in a naturally aged rat model. Young Wistar rats, treated with D-gal (1200 mg/week), and old rats received daily WK or WSE added to the feed. After 8 weeks, blood, liver, and brain samples were collected and hematological, biochemical, oxidative stress biomarkers, histological, and immunohistochemical analyses were performed. Moreover, acetylcholinesterase activity was investigated in brain homogenates. The outcomes demonstrated significant improvement in cellular antioxidant activity and/or decrease of reactive oxygen species, advanced glycation end products, nitric oxide, malondialdehyde, or increase of glutathione after WK or WSE intake in both models. Additionally, WSE showed hypoglycemic effect, and both WK and WSE lowered acetylcholinesterase activity. Both diets could protect neurons against the induced senescence and could reverse the pathological conditions in the physiological aged brain. Thus, dietary supplementation with WK or WSE can maintain the liver and brain health and reduce the risk of age-related diseases, as well as delaying the onset of aging processes.