Involvement of Metabolic Lipid Mediators in the Regulation of Apoptosis

Apoptosis is the physiological mechanism of cell death and can be modulated by endogenous and exogenous factors, including stress and metabolic alterations. Reactive oxygen species (ROS), as well as ROS-dependent lipid peroxidation products (including isoprostanes and reactive aldehydes including 4-hydroxynonenal) are proapoptotic factors. These mediators can activate apoptosis via mitochondrial-, receptor-, or ER stress-dependent pathways. Phospholipid metabolism is also an essential regulator of apoptosis, producing the proapoptotic prostaglandins of the PGD and PGJ series, as well as the antiapoptotic prostaglandins of the PGE series, but also 12-HETE and 20-HETE. The effect of endocannabinoids and phytocannabinoids on apoptosis depends on cell type-specific differences. Cells where cannabinoid receptor type 1 (CB1) is the dominant cannabinoid receptor, as well as cells with high cyclooxygenase (COX) activity, undergo apoptosis after the administration of cannabinoids. In contrast, in cells where CB2 receptors dominate, and cells with low COX activity, cannabinoids act in a cytoprotective manner. Therefore, cell type-specific differences in the pro- and antiapoptotic effects of lipids and their (oxidative) products might reveal new options for differential bioanalysis between normal, functional, and degenerating or malignant cells, and better integrative biomedical treatments of major stress-associated diseases

Protective Effect of Blackcurrant on Liver Cell Membrane of Rats Intoxicated with Ethanol

Chronic ethanol intoxication oxidative stress participates in the development of many diseases. Nutrition and the interaction of food nutrients with ethanol metabolism may modulate alcohol toxicity. One such compound is blackcurrant, which also has antioxidant abilities. We investigated the effect of blackcurrant as an antioxidant on the composition and electrical charge of liver cell membranes in ethanol-intoxicated rats. Qualitative and quantitative phospholipid composition and the presence of integral membrane proteins were determined by high-performance liquid chromatography. Electrophoresis was used to determine the surface charge density of the rat liver cell membranes. Ethanol intoxication is characterized by changes in cell metabolism that alter the structure and function of cell membrane components. Ethanol increased phospholipid levels and altered the level of integral proteins as determined by decreased phenylalanine, cysteine, and lysine. Ethanol significantly enhanced changes in the surface charge density of the liver cell membranes. Administration of blackcurrant to rats intoxicated with ethanol significantly protected lipids and proteins against oxidative modifications. It is possible that the beneficial effect of blackcurrant is connected with its abilities to scavenge free radicals and to chelate metal ions

Green tea as an antioxidant which protects against alcohol induced injury in rats - a histopathological examination

Our study with animal models was designed to test the hypothesis that green tea protects against chronic (over 4 weeks) alcohol induced liver injury in rats. The research was conducted on Wistar male rats divided into 4 research groups: I - received the Libera-De Carli control diet (L-DC), II - received (L-DC) and green tea, III - received (L-DC) and ethanol and IV - received (L-DC), green tea and ethanol. When comparing groups I and II we saw less intensive steatosis in group II than in group I, which can suggest that green tea may affect the accumulation of fat in the hepatocytes and protect them against steatosis and disruption. In III, the ethanol group, the steatosis of the liver increased considerably and the green tea which was given with ethanol in group IV did not halt this, as in group IV we also observed intensive steatosis in the liver. From this data we conclude that green tea has an important, although not fully understood role in preventing liver injury

Ocena równowagi utleniająco-przeciwutleniającej w ścianie i skrzeplinie przyściennej

Background. The aim of the study was to evaluate the activity of the key antioxidative enzyme - superoxide dismutase (SOD) and the content of the lipid peroxidation product - malondialdehyde (MDA) in the wall and mural thrombus of abdominal aortic aneurysms. Material and methods. The studied material consisted of aneurysm walls and mural thrombi obtained during surgery from 36 patients. The aneurysm wall was stratified into the inner layer and the outer part, which was composed of media and adventitia. Mural thrombus was stratified into the external part - adhering to the aneurysm wall and the internal part - being in touch with blood. Aortas from organ donors served as controls. SOD activity was assessed according to Sykes method, whereas MDA content according to HPLC method in tissue homogenates. Results. The lowest superoxide dismutase activity was found in the aneurysm wall. Furthermore, its inner layer showed 50% lower enzyme activity than the outer one. Superoxide dismutase activity was significantly higher in thrombus when compared to the aneurysm wall with a particular increase in its internal part. The highest MDA content was found in thrombus (without significant differences between its parts). The inner layer of the aneurysm wall showed more than a twofold higher MDA content than its outer layer. The lowest MDA content was found in the wall of normal aorta. Conclusions. Diminished activity of the key antioxidant enzyme - SOD in the aneurysm wall, particularly in its inner layer, favours free radical generation, oxidative stress development and consequently intensive lipid peroxidation. This process affects structural changes of the aneurysm wall.Wstęp. Celem badań było poznanie aktywności podstawowego enzymu antyoksydacyjnego - dysmutazy ponadtlenkowej (SOD) oraz stężenia produktu peroksydacji lipidów - malonylodialdehydu (MDA) w ścianie oraz skrzeplinie przyściennej tętniaka aorty brzusznej. Materiał i metody. Materiał do badań stanowiły ściany tętniaków aorty brzusznej oraz skrzepliny przyścienne pobrane podczas operacji od 36 chorych. Ścianę tętniaka dzielono na warstwę wewnętrzną oraz część zewnętrzną zawierającą warstwę środkową i zewnętrzną. Od skrzepliny oddzielano część zewnętrzną - przylegającą do ściany tętniaka oraz wewnętrzną, mającą kontakt z krwią. Grupę kontrolną stanowiły aorty pobrane od dawców narządów. W homogenatach oznaczono aktywność SOD metodą Sykesa oraz zawartość MDA, wykorzystując HPLC. Wyniki. Najniższą aktywność SOD stwierdzono w ścianie tętniaka, przy czym w warstwie wewnętrznej ściany zanotowano aktywność o ponad 50% niższą niż w warstwie zewnętrznej. W skrzeplinie aktywność SOD była istotnie wyższa niż w ścianie tętniaka. W warstwie wewnętrznej skrzepliny aktywność SOD była większa niż w warstwie zewnętrznej. Najwyższą zawartość MDA stwierdzono w skrzeplinie przyściennej (bez istotnych różnic między warstwami). Warstwa wewnętrzna ściany tętniaka zawierała ponad 2-krotnie więcej MDA niż warstwa zewnętrzna. Najmniejszą zawartość MDA zaobserwowano w ścianie aorty dawcy. Wnioski. Występowanie obniżonej aktywności kluczowego antyoksydacyjnego enzymu SOD w ścianie tętniaka aorty, zwłaszcza jego warstwy wewnętrznej, sprzyja tworzeniu rodników tlenowych, powstawaniu stresu oksydacyjnego i w konsekwencji - nasilonej peroksydacji lipidów. Wpływa to na zmiany struktury ściany tętniaka

Disease-dependent antiapoptotic effects of cannabidiol for keratinocytes observed upon UV irradiation

Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ2 level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ2, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD

Oxidative Stress and Lipid Mediators Modulate Immune Cell Functions in Autoimmune Diseases

Autoimmune diseases, including psoriasis, systemic lupus erythematosus (SLE), and rheumatic arthritis (RA), are caused by a combination of environmental and genetic factors that lead to overactivation of immune cells and chronic inflammation. Since oxidative stress is a common feature of these diseases, which activates leukocytes to intensify inflammation, antioxidants could reduce the severity of these diseases. In addition to activating leukocytes, oxidative stress increases the production of lipid mediators, notably of endocannabinoids and eicosanoids, which are products of enzymatic lipid metabolism that act through specific receptors. Because the anti-inflammatory CB2 receptors are the predominant cannabinoid receptors in leukocytes, endocannabinoids are believed to act as anti-inflammatory factors that regulate compensatory mechanisms in autoimmune diseases. While administration of eicosanoids in vitro leads to the differentiation of lymphocytes into T helper 2 (Th2) cells, eicosanoids are also necessary for the different0iation of Th1 and Th17 cells. Therefore, their antagonists and/or the genetic deletion of their receptors abolish inflammation in animal models of psoriasis—RA and SLE. On the other hand, products of non-enzymatic lipid peroxidation, especially acrolein and 4-hydroxynonenal-protein adducts, mostly generated by an oxidative burst of granulocytes, may enhance inflammation and even acting as autoantigens and extracellular signaling molecules in the vicious circle of autoimmune diseases

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

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-∆12, 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