scholarly journals Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 159 ◽  
Author(s):  
Ewa Ambrożewicz ◽  
Piotr Wójcik ◽  
Adam Wroński ◽  
Wojciech Łuczaj ◽  
Anna Jastrząb ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lipid Metabolism ◽  
Psoriatic Arthritis ◽  
Psoriasis Vulgaris ◽  
Redox Signaling ◽  
Heme Oxygenase 1 ◽  
Lipid Peroxidation Products ◽  
Redox Imbalance ◽  
Enhanced Activity

Inflammatory granulocytes are characterized by an oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on a systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important yet not fully understood roles in the pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidases in granulocytes with a decrease of enzymatic and non-enzymatic antioxidants in the plasma of psoriatic patients. The nuclear factor erythroid 2–related factor 2 (Nrf2) and its regulators were increased in both forms of psoriasis while heme oxygenase 1 levels were increased only in psoriasis vulgaris. The redox imbalance was associated with decreased levels of phospholipids and of free polyunsaturated fatty acids but with enhanced activity of enzymes involved in lipid metabolism (phospholipase A2, acetylhydrolase PAF, cyclooxygenases 1 and 2) and increased lipid peroxidation products 4-hydroxynonenal, isoprostanes, and neuroprostanes. Increased endocannabinoids and G protein-coupled receptor 55 were observed in both forms of the disease while expression of the cannabinoid type 1 receptor (CB1) was increased only in patients with psoriatic arthritis, which is opposite to the cannabinoid type 2 receptor. This receptor was increased only in psoriasis vulgaris. Changes in protein expression promoted the apoptosis of granulocytes by increased caspases mainly in psoriasis vulgaris. This study indicates that inhibition of the Nrf2 pathway in psoriatic arthritis promotes a redox imbalance. In addition, increased expression of CB1 receptors leads to increased oxidative stress, lipid modifications, and inflammation, which, in turn, may promote the progression of psoriasis into the advanced, arthritic form of the disease.

scholarly journals Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

2018 ◽  
Author(s):  
Ewa Ambrożewic ◽  
Piotr Wojcik ◽  
Adam Wronski ◽  
Wojciech Luczaj ◽  
Anna Jastrząb ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lipid Metabolism ◽  
Psoriatic Arthritis ◽  
Psoriasis Vulgaris ◽  
Redox Signaling ◽  
Lipid Peroxidation Product ◽  
Lipid Peroxidation Products ◽  
Redox Imbalance ◽  
Enhanced Activity

Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

scholarly journals Kaempferol and Kaempferide Attenuate Oleic Acid-Induced Lipid Accumulation and Oxidative Stress in HepG2 Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8847
Author(s):  
Fangfang Tie ◽  
Jin Ding ◽  
Na Hu ◽  
Qi Dong ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Lipid Metabolism ◽  
Western Blot ◽  
Blot Analysis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Heme Oxygenase 1 ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which lacks ideal treatment options. Kaempferol and kaempferide, two natural flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of kaempferol and kaempferide on oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of NAFLD. The results indicated an increased accumulation of lipid droplets and triacylglycerol (TG) by OA, which was attenuated by kaempferol and kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that kaempferol and kaempferide reduced expression of lipogenesis-related proteins, including sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1). Expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic transcription factors, was also decreased by kaempferol and kaempferide treatment. In addition, western blot analysis also demonstrated that kaempferol and kaempferide reduced expression of heme oxygenase-1 (HO-1) and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of kaempferol and kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that kaempferol and kaempferide could attenuate OA-induced lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of NAFLD.

scholarly journals Local and systemic oxidative stress in chronic suppurative otitis media

2021 ◽  
pp. 148-156
Author(s):  
I. D. Dubinets ◽  
M. Yu. Korkmazov ◽  
A. I. Sinitskii ◽  
E. I. Danshova ◽  
I. N. Skirpichnikov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Surgical Treatment ◽  
Temporal Bone ◽  
Otitis Media ◽  
Local Level ◽  
Chronic Suppurative Otitis Media ◽  
Suppurative Otitis Media ◽  
Lipid Peroxidation Products ◽  
Systemic Level

Introduction. According to the literature, oxidative stress is described as one of the main factors in the pathogenesis of chronic suppurative otitis media, supporting the inflammatory process at the local level. The transition of inflammatory mediators to the systemic level is associated with the risk of developing ear purulent-destructive complications. The study of the products of lipid peroxidation in comparison with morphological changes in the structures of the temporal bone will justify the tactics of the operation.Aim. Comparison of the levels of lipid peroxidation products at the local and systemic levels in chronic suppurative otitis media, depending on the nature of pathomorphological changes in the structures of the temporal bone.Materials and methods. A prospective study of 130 patients with chronic suppurative otitis media at the age of 20-62 years with a verified diagnosis of chronic suppurative otitis media, admitted for surgical treatment, was carried out. To study the indicators of oxidative stress at the systemic level, the blood serum of patients was used; at the local level, the bone biomaterial obtained from patients during the surgical treatment of chronic suppurative otitis media was used. The quantitative determination of the primary, secondary and final products of peroxidation was carried out in the groups of patients with separate registration of lipoperoxides in the heptane and isopropanol phases of the lipid extract by spectrophotometry.Results and discussion. In the observation of patients with morphological signs of purulent destruction of the temporal bone, not only a local level of inflammation activity, but also a systemic level of an unfavorable outcome was revealed in two variants: osteoproliferation or osteonecrosis of the bone tissue of the temporal bone in chronic purulent otitis media with a constant threat to the patient's life due to intracranial purulent complications.Conclusion. The appearance in low concentrations of lipid peroxidation products in serum in patients with chronic purulent otitis media substantiates the need for a behind-the-ear approach in reconstructive-sanitizing otosurgery even with minimal clinical manifestations and CT scan data, since at the preclinical level it confirms the osteonecrotic type of bone remodeling with the risk of delayed death.

scholarly journals Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis

2019 ◽  
Vol 20 (17) ◽  
pp. 4249 ◽  
Author(s):  
Piotr Wójcik ◽  
Michał Biernacki ◽  
Adam Wroński ◽  
Wojciech Łuczaj ◽  
Georg Waeg ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Psoriatic Arthritis ◽  
Stress Responses ◽  
Psoriasis Vulgaris ◽  
Mononuclear Cells ◽  
Leukotriene B4 ◽  
Cyclooxygenase 1 ◽  
Hydroxyoctadecadienoic Acid ◽  
Altered Lipid ◽  
Cox 1

The aim of this study was to investigate possible stress-associated disturbances in lipid metabolism in mononuclear cells, mainly lymphocytes of patients with psoriasis vulgaris (Ps, n = 32) or with psoriatic arthritis (PsA, n = 16) in respect to the healthy volunteers (n = 16). The results showed disturbances in lipid metabolism of psoriatic patients reflected by different phospholipid profiles. The levels of non-enzymatic lipid metabolites associated with oxidative stress 8-isoprostaglandin F2α (8-isoPGF2α) and free 4-hydroxynonenal (4-HNE) were higher in PsA, although levels of 4-HNE-His adducts were higher in Ps. In the case of the enzymatic metabolism of lipids, enhanced levels of endocannabinoids were observed in both forms of psoriasis, while higher expression of their receptors and activities of phospholipases were detected only in Ps. Moreover, cyclooxygenase-1 (COX-1) activity was enhanced only in Ps, but cyclooxygenase-2 (COX-2) was enhanced both in Ps and PsA, generating higher levels of eicosanoids: prostaglandin E1 (PGE1), leukotriene B4 (LTB4), 13-hydroxyoctadecadienoic acid (13HODE), thromboxane B2 (TXB2). Surprisingly, some of major eicosanoids 15-d-PGJ2 (15-deoxy-Δ12,14-prostaglandin J2), 15-hydroxyeicosatetraenoic acid (15-HETE) were elevated in Ps and reduced in PsA. The results of our study revealed changes in lipid metabolism with enhancement of immune system-modulating mediators in psoriatic mononuclear cells. Evaluating further differential stress responses in Ps and PsA affecting lipid metabolism and immunity might be useful to improve the prevention and therapeutic treatments of psoriasis.

scholarly journals Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3231 ◽  
Author(s):  
Ling Hu ◽  
Kuan Tian ◽  
Tao Zhang ◽  
Chun-Hua Fan ◽  
Peng Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Protein Modification ◽  
Density Lipoprotein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Uremic Toxin ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Abnormal Lipid Metabolism

Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5′monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.

Antioxidant Responses and Lipid Peroxidation of Penaeus Indicus Postlarvae Subjected to Sublethal Copper Exposure

Crustaceana ◽  
2011 ◽  
Vol 84 (10) ◽  
pp. 1197-1210 ◽  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Copper Toxicity ◽  
Sod Activity ◽  
Lipid Peroxidation Products ◽  
Coastal Marine ◽  
Potential Biomarker ◽  
Penaeus Indicus

AbstractThe objective of this study was to determine the effect of sublethal copper concentrations on certain antioxidant enzymes and lipid peroxidation products in the postlarvae (PL) of Penaeus indicus when subjected to short- and long-term exposure in the laboratory. The PL of P. indicus were exposed to 0.1641 ppm (sublethal) copper for a period of 30 days along with a parallel control. Sampling was carried out at six different time intervals, i.e., 24, 48, and 96 hrs (shortterm), and 10, 20, and 30 days (long-term). Variations in the activity of the antioxidant enzymes, namely, catalase (CAT) and superoxide dismutase (SOD), as well as lipid peroxidation products (LPP) were measured as biomarkers of metal toxicity. Our results showed a significant (P < 0.05) increase in LPP (indicating oxidative stress) and CAT activity (indicating an adaptive response of the PL for protection against oxidative stress) in the exposed PL for all periods of exposure. However, SOD activity significantly (P < 0.05) decreased on 20 and 30 days exposure, indicating susceptibility of the PL to oxidative stress upon long-term exposure. Therefore, CAT can serve as a better biomarker of oxidative stress than SOD to long-term copper toxicity. Our results indicate that copper contamination causes oxidative stress even at sublethal doses in Penaeus indicus PL, which can thus be used as a potential biomarker of copper toxicity for long-term monitoring of coastal marine ecosystems.

Application of lipid peroxidation products as biomarkers for flutamide-induced oxidative stress in vitro

2015 ◽  
Vol 238 (3) ◽  
pp. 53-59 ◽  
Author(s):  
Marieke Teppner ◽  
Franziska Böss ◽  
Beat Ernst ◽  
Axel Pähler
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Lipid Peroxidation Products
Sign in / Sign up

Export Citation Format

Share Document