Oxysterols Increase Inflammation, Lipid Marker Levels and Reflect Accelerated Endothelial Dysfunction in Experimental Animals

Objective. Oxidized cholesterol derivatives are thought to exert atherogenic effect thus adversely affecting vascular endothelium. The aim of the study was to assess the effect of 5α,6α-epoxycholesterol on experimentally induced hypercholesterolemia in rabbits, and the levels of homocysteine (HCY), asymmetric dimethylarginine (ADMA), paraoxonase-1 (PON-1), and inflammatory parameters (IL-6, TNF-α, CRP). Material and methods. The rabbits were divided into 3 groups, 8 animals each, and fed with basic fodder (C), basic fodder plus cholesterol (Ch) or basic fodder plus 5α,6α-epoxycholesterol, and unoxidized cholesterol (ECh). Serum concentrations of studied parameters were determined at 45-day intervals. The study was continued for six months. Results. We demonstrated that adding 5α,6α-epoxycholesterol to basic fodder significantly affected lipid status of the experimental animals, increasing total cholesterol and LDL cholesterol levels, as well as HCY and ADMA levels, whilst leaving the PON-1 activity unaffected. Additionally, the ECh group presented with significantly higher concentrations of inflammatory biomarkers (IL-6, TNF-α, and CRP). In the Ch group, lower yet significant (as compared to the C group) changes of levels of studied parameters were observed. Conclusion. Exposure of animals with experimentally induced hypercholesterolemia to 5α,6α-epoxycholesterol increases dyslipidaemia, endothelial dysfunction, and inflammatory response

5α,6α-Epoxyphytosterols and 5α,6α-Epoxycholesterol Increase Oxidative Stress in Rats on Low-Cholesterol Diet

Objective. Cholesterol oxidation products have an established proatherogenic and cytotoxic effect. An increased exposure to these substances may be associated with the development of atherosclerosis and cancers. Relatively little, though, is known about the effect of phytosterol oxidation products, although phytosterols are present in commonly available and industrial food products. Thus, the aim of the research was to assess the effect of 5α,6α-epoxyphytosterols, which are important phytosterol oxidation products, on redox state in rats. Material and Methods. The animals were divided into 3 groups and exposed to nutritional sterols by receiving feed containing 5α,6α-epoxyphytosterols (ES group) and 5α,6α-epoxycholesterol (Ech group) or sterol-free feed (C group). The levels of malondialdehyde (MDA), conjugated dienes (CD), and ferric reducing antioxidant potential (FRAP) were assayed in the plasma; anti-7-ketocholesterol antibodies and activity of paraoxonase-1 (PON1) were determined in serum, whereas the activity of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), S-glutathione transferase (GST), and superoxide dismutase (SOD) were assayed in RBCs. Results. During the experiment, the levels of lipid peroxidation products increased, such as CD and anti-7-ketocholesterol antibodies. At the same time, the plasma levels of FRAP and serum activity of PON1 decreased alongside the reduced activity of GPx, GR, and SOD in RBCs. There was no effect of the studied compounds on the plasma MDA levels or on the activity of CAT and GST in RBCs. Conclusions. Both 5α,6α- epoxyphytosterols and 5α,6α-epoxycholesterols similarly dysregulate the redox state in experimental animal model and may significantly impact atherogenesis

5α,6α-Epoxyphytosterols and 5α,6α-Epoxycholesterol Increase Nitrosative Stress and Inflammatory Cytokine Production in Rats on Low-Cholesterol Diet

Objective. Oxidized cholesterol derivatives are compounds with proven atherogenic and mutagenic effects. However, little is known about the effect of oxidized plant sterol derivatives (oxyphytosterols), whose structure is similar to the one of oxycholesterols. Our previous studies indicate that they have a similar profile of action, e.g., both exacerbate disorder of lipid metabolism and oxidative stress in experimental animals. The aim of the present study was to assess the effect of epoxycholesterol and epoxyphytosterols (mainly sitosterol) on the severity of nitrosative stress and the concentration of selected proinflammatory cytokines in blood and liver tissue of rats on a low-cholesterol diet. Material and Methods. Forty-five male Wistar rats were fed with feed containing 5α,6α-epoxyphytosterols (ES group, n: 15), 5α,6α-epoxycholesterol (ECh group, n: 15), and oxysterol-free feed (C group, n: 15) for 90 days (daily dose of oxysterols: 10 mg/kg). At the end of the experiment, nitrotyrosine, TNF-α, IL-1β, IL-6, and lipid metabolism parameters were determined in blood serum. Furthermore, nitrotyrosine, TNF-α, cholesterol, and triglyceride content were determined in liver homogenates. Results. Serum nitrotyrosine, IL-1β, and TNF-α concentrations as well as TNF-α content in the liver were significantly higher in both groups exposed to oxysterols (ECh and ES groups) as compared to the C group. The serum IL-6 level and nitrotyrosine content in the liver were significantly higher in the ECh group, as compared to the C and ES groups. There was evidence to support the dyslipidemic effect of studied compounds. Conclusions. The results indicate that oxidized plant sterols have a similar toxicity profile to that of oxycholesterols, including nitrosative stress induction, proinflammatory effect, and impaired lipid metabolism

Oxysterols Increase Inflammation, Lipid Marker Levels and Reflect Accelerated Endothelial Dysfunction in Experimental Animals

Objective. Oxidized cholesterol derivatives are thought to exert atherogenic effect thus adversely affecting vascular endothelium. The aim of the study was to assess the effect of 5α,6α-epoxycholesterol on experimentally induced hypercholesterolemia in rabbits, and the levels of homocysteine (HCY), asymmetric dimethylarginine (ADMA), paraoxonase-1 (PON-1), and inflammatory parameters (IL-6, TNF-α, CRP). Material and methods. The rabbits were divided into 3 groups, 8 animals each, and fed with basic fodder (C), basic fodder plus cholesterol (Ch) or basic fodder plus 5α,6α-epoxycholesterol, and unoxidized cholesterol (ECh). Serum concentrations of studied parameters were determined at 45-day intervals. The study was continued for six months. Results. We demonstrated that adding 5α,6α-epoxycholesterol to basic fodder significantly affected lipid status of the experimental animals, increasing total cholesterol and LDL cholesterol levels, as well as HCY and ADMA levels, whilst leaving the PON-1 activity unaffected. Additionally, the ECh group presented with significantly higher concentrations of inflammatory biomarkers (IL-6, TNF-α, and CRP). In the Ch group, lower yet significant (as compared to the C group) changes of levels of studied parameters were observed. Conclusion. Exposure of animals with experimentally induced hypercholesterolemia to 5α,6α-epoxycholesterol increases dyslipidaemia, endothelial dysfunction, and inflammatory response

Saliva-Based Protein Analysis in Pediatric Dentofacial Inflammation

Bogusława Orzechowska-Wylęgała,1 Adam Wylęgała,2 Jolanta Zalejska Fiolka,3 Zenon Czuba,4 Michal Toborek5 1Department of Pediatric Otolaryngology, Head and Neck Surgery, Chair of Pediatric Surgery, Medical University of Silesia (SUM), Katowice, Poland; 2Health Promotion and Obesity Management, Department of Pathophysiology in Katowice, SUM, Katowice, Poland; 3Department of Biochemistry Faculty of Medical Science in Zabrze, SUM, Katowice, Poland; 4Department and Division of Microbiology and Immunology in Zabrze, SUM, Katowice, Poland; 5Department of Biochemistry and Molecular Biology, University of Miami, School of Medicine, Miami, FL, USACorrespondence: Bogusława Orzechowska-Wylęgała, Email [email protected]: Saliva contains various proteins that are important in developing inflammatory processes and their prevention. One key aspect of saliva research is the relationship between oral infections and inflammation, and the role of some salivary proteins.The Work Aims: To demonstrate which salivary cytokines can be biomarkers of acute odontogenic oral and facial infections in children.Material and Methods: The study included two groups of patients: a study group of 28 children: 7 girls and 21 boys aged 3 − 17 years with acute dentofacial inflammation (DI) and a control group of 52 children: 16 girls and 36 boys aged 4– 17 years with uncomplicated dental caries (CE). The levels of Interleukin-5 (IL-5), Interleukin − 10 (IL-10), Interleukin-17A (IL-17A), Interleukin-12p70 (IL-12p70), Eotaxin, Rantes, Vascular Endothelial Growth Factor (VEGF), and Interferon gamma-induced protein 10 (IP10) in the saliva of children in DI and CE groups were compared. Statistical analysis was performed with Statistica 13. The Student’s t-test and the Wilcoxon signed-rank test were used.Results: The results show that IL-10, IL-17A, and Eotaxin showed a statistically significant increase in the DI group compared to the CE group. The significance level for IL-10 was p=0.02, for IL-17A was equal to Eotaxin and p=0.04. The other measured parameters did not differ statistically significant between the two groups.Conclusion: IL-10, IL-17A, and Eotaxin can be used as potential biomarkers for tooth-related inflammatory states of the oral cavity and face in children. These biomarkers can be useful in identifying and monitoring the presence of inflammation in the oral cavity and face.Keywords: salivary cytokines and chemokines, odontogenic oral and facial inflammation, childre

Effect of treatment with N-acetylcysteine on non-enzymatic antioxidant reserves and lipid peroxidation in workers exposed to lead

There are no published studies examining the effects of N-acetylcysteine (NAC) administration on the non-enzymatic defence systems in humans exposed to lead. In view of this, it was decided to measure the levels of uric acid (UA), albumin, bilirubin and alpha-tocopherol before and after treatment with NAC. An estimation was also made of the degree of oxidative stress by measuring the ferric reducing ability of plasma (FRAP), the levels of conjugated dienes (CD) and lipid hydroperoxides (LHP). Male employees who worked with lead were randomized into two groups. The first group included workers who were not administered any drugs (n=49), while the second group (n=122) consisted of workers who were treated with NAC at three different doses (200 mg, 400 mg and 800 mg) for 12 weeks. The administration of NAC (400 mg, 800 mg) resulted in significant decreases in the LHP levels. Similarly, a strong tendency toward lower levels of CD was observed in the same groups. The UA levels were significantly lower only in the group receiving the 200 mg dose of NAC. However, the alpha-tocopherol levels were significantly elevated after treatment with NAC (400 mg, 800 mg). NAC administration did not significantly affect the levels of bilirubin and albumin, but a tendency toward higher values was observed for FRAP. NAC reduced the extent of lipid peroxidation in a dose-dependent manner. Elevated concentrations of alpha-tocopherol may have enhanced the beneficial effects of NAC. Treatment with NAC may contribute to the restoration of non-enzymatic antioxidant reserves when administered to lead-exposed workers