Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions.

Cancer is one of the most serious public health issues worldwide, demanding ongoing efforts to find novel therapeutic agents and approaches. Amid growing interest in the oncological applications of phytochemicals, particularly polyphenols, resveratrol-a naturally occurring polyphenolic stilbene derivative-has emerged as a candidate of interest. This review analyzes the pleiotropic anti-cancer effects of resveratrol, including its modulation of apoptotic pathways, cell cycle regulation, inflammation, angiogenesis, and metastasis, its interaction with cancer stem cells and the tumor microenvironment. The effects of resveratrol on mitochondrial functions, which are crucial to cancer development, are also discussed. Future research directions are identified, including the elucidation of specific molecular targets, to facilitate the clinical translation of resveratrol in cancer prevention and therapy.

Effect of Organic Selenium on the Homeostasis of Trace Elements, Lipid Peroxidation, and mRNA Expression of Antioxidant Proteins in Mouse Organs.

(1) In this study we determined the effect of long-term selenomethionine administration on the oxidative stress level and changes in antioxidant protein/enzyme activity; mRNA expression; and the levels of iron, zinc, and copper. (2) Experiments were performed on 4-6-week-old BALB/c mice, which were given selenomethionine (0.4 mg Se/kg b.w.) solution for 8 weeks. The element concentration was determined via inductively coupled plasma mass spectrometry. mRNA expression of SelenoP, Cat, and Sod1 was quantified using real-time quantitative reverse transcription. Malondialdehyde content and catalase activity were determined spectrophotometrically. (3) After long-term SeMet administration, the amount of Se increased by 12-fold in mouse blood, 15-fold in the liver, and 42-fold in the brain, as compared to that in the control. Exposure to SeMet decreased amounts of Fe and Cu in blood, but increased Fe and Zn levels in the liver and increased the levels of all examined elements in the brain. Se increased malondialdehyde content in the blood and brain but decreased it in liver. SeMet administration increased the mRNA expression of selenoprotein P, dismutase, and catalase, but decreased catalase activity in brain and liver. (4) Eight-week-long selenomethionine consumption elevated Se levels in the blood, liver, and especially in the brain and disturbed the homeostasis of Fe, Zn, and Cu. Moreover, Se induced lipid peroxidation in the blood and brain, but not in the liver. In response to SeMet exposure, significant up-regulation of the mRNA expression of catalase, superoxide dismutase 1, and selenoprotein P in the brain, and especially in the liver, was determined.

The Difference of Cholesterol, Platelet and Cortisol Levels in Patients Diagnosed with Chronic Heart Failure with Reduced Ejection Fraction Groups According to Neutrophil Count.

Background and Objectives: It is known that neutrophils are involved in the pro-inflammatory processes and thus, can have a great impact on the pathophysiology of heart failure (HF). Moreover, hypercholesterolemia heightens neutrophil production, thereby accelerating cardiovascular inflammation. However, there is a lack of information about the relation of low inflammation to the state of stress, hypercholesterolemia, and pro-thrombotic statement in patients with chronic HF. Therefore, we aimed to determine whether platelet, cholesterol and cortisol levels differ in a different inflammatory condition groups according to the neutrophil count in patients diagnosed with CHF with reduced ejection fraction (CHFrEF), and whether there is a correlation between those readings. Materials and Methods: The average of neutrophil count was 4.37 × 109 L; therefore, 180 patients were separated into two groups: one with relatively a higher inflammatory environment (neutrophil count ≥ 4.37 × 109 L (n = 97)) and one with a relatively lower inflammatory environment (neutrophil count < 4.38 × 109 L (n = 83)). We also determined the levels of lymphocytes, monocytes, platelet count (PLT), mean platelet volume (MPV), platelet aggregation, the levels of cortisol and cholesterol and the concentrations of C reactive protein (CRP) and fibrinogen. Results: We found that CRP, fibrinogen and cortisol concentrations were statistically significantly higher in the group with higher neutrophil counts. However, there were no differences among cholesterol concentration and other markers of platelet function between the groups. We also showed that PLT, leukocyte and monocyte counts were higher in the group with a higher neutrophil count, and the PLT correlated with other cell type count and CRP. In addition, the neutrophil count correlated with concentrations of fibrinogen, evening cortisol and CRP. Conclusions: Cortisol, fibrinogen and CRP levels, PLT and monocyte counts were higher in the CHFrEF patient group with higher neutrophil counts. The cholesterol levels and platelet function readings did not differ between the groups. The neutrophil count correlated with evening cortisol concentration.

Platelet Activity and Its Correlation with Inflammation and Cell Count Readings in Chronic Heart Failure Patients with Reduced Ejection Fraction.

Background and objectives: There has been an increasing interest in the role of inflammation in thrombosis complications in chronic heart failure (HF) patients. The incidence of thrombosis in HF has been shown to be the highest in patients classified as NYHA IV (New York Heart association). It is stated that inflammation is regulated by platelet-induced activation of blood leukocytes. We aimed to compare the platelet and cell count readings in chronic HF with reduced ejection fraction (HFrEF) patients according to NYHA functional class and to evaluate the correlation between those readings. Materials and methods: A total of 185 patients were examined. The results of heart echoscopy (TEE) testing; fibrinogen, N-terminal pro b-type natriuretic peptide (NT-proBNP), C reactive protein (CRP), and cortisol concentrations; complete blood counts; and a 6 min walking test were assessed and platelet aggregation was determined. Results: Mean platelet volume (MPV) increased with deterioration of a patient's state (p < 0.005). Lymphocyte count and percentage were the lowest in the NYHA IV group (p < 0.005). Neutrophil and monocyte percentage and count were the highest (p < 0.045) in the NYHA IV group. Adenosine diphosphate (ADP)- and ADR-induced platelet aggregation was higher in the NYHA III group compared to NYHA II and I groups (p < 0.023). NYHA functional class correlated with mean platelet volume (MPV) (r = 0.311, p = 0.0001), lymphocyte count (r = -0.186, p = 0.026), monocyte count (p = 0.172, p = 0.041), and percentage (r = 0.212, p = 0.011). CRP concentration correlated with NT-proBNP (r = 0.203, p = 0.005). MPV correlated with fibrinogen concentration (r = 0.244, p = 0.004). Conclusions: (1) MPV could be considered as an additional reading reflecting a patient's condition, however the use of MPV to identify patients at risk of hypercoagulable state should be evaluated in more extensive studies; (2) increased neutrophil and monocyte counts could indicate a higher inflammatory state in chronic HFrEF.

Fatty Acid Oxidation and Mitochondrial Morphology Changes as Key Modulators of the Affinity for ADP in Rat Heart Mitochondria.

Fatty acids are the main respiratory substrates important for cardiac function, and their oxidation is altered during various chronic disorders. We investigated the mechanism of fatty acid-oxidation-induced changes and their relations with mitochondrial morphology and ADP/ATP carrier conformation on the kinetics of the regulation of mitochondrial respiration in rat skinned cardiac fibers. Saturated and unsaturated, activated and not activated, long and medium chain, fatty acids similarly decreased the apparent KmADP. Addition of 5% dextran T-70 to mimic the oncotic pressure of the cellular cytoplasm markedly increased the low apparent KmADP value of mitochondria in cardiac fibers respiring on palmitoyl-l-carnitine or octanoyl-l-carnitine, but did not affect the high apparent KmADP of mitochondria respiring on pyruvate and malate. Electron microscopy revealed that palmitoyl-l-carnitine oxidation-induced changes in the mitochondrial ultrastructure (preventable by dextran) are similar to those induced by carboxyatractyloside. Our data suggest that a fatty acid oxidation-induced conformational change of the adenosine diphosphate (ADP)/adenosine triphosphate (ATP) carrier (M-state to C-state, condensed to orthodox mitochondria) may affect the oxidative phosphorylation affinity for ADP.

Selenium Anticancer Properties and Impact on Cellular Redox Status.

(1) Background: In this review, we provide information published in recent years on the chemical forms, main biological functions and especially on antioxidant and prooxidant activities of selenium. The main focus is put on the impact of selenoproteins on maintaining cellular redox balance and anticancerogenic function. Moreover, we summarize data on chemotherapeutic application of redox active selenium compounds. (2) Methods: In the first section, main aspects of metabolism and redox activity of selenium compounds is reviewed. The second outlines multiple biological functions, asserted when selenium is incorporated into the structure of selenoproteins. The final section focuses on anticancer activity of selenium and chemotherapeutic application of redox active selenium compounds as well. (3) Results: optimal dietary level of selenium ensures its proper antioxidant and anticancer activity. We pay special attention to antioxidant activities of selenium compounds, especially selenoproteins, and their importance in antioxidant defence. It is worth noting, that data on selenium anticancer properties is still contraversive. Moreover, selenium compounds as chemotherapeutic agents usually are used at supranutritional doses. (4) Conclusions: Selenium play a vital role for many organism systems due to its incorporation into selenoproteins structure. Selenium possesses antioxidant activity at optimal doses, while at supranutritional doses, it displays prooxidant activity. Redox active selenium compounds can be used for cancer treatment; recently special attention is put to selenium containing nanoparticles.

Multiplicity of effects and health benefits of resveratrol.

Resveratrol is mainly found in grapes and red wine, also in some plants and fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries. Moreover, nowadays this compound is available as purified preparation and dietary supplement. Resveratrol provides a wide range of benefits, including cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood glucose-lowering and anticancer activities, hence it exhibits a complex mode of action. During the recent years, these properties have been widely studied in animal and human models, both in vitro and in vivo. This paper is intended to present information published during the recent years on the biological activities and multiple effects of resveratrol.

The effect of Leonurus cardiaca herb extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.

Motherwort (Leonurus cardiaca) possesses antibacterial, antioxidant, anti-inflammatory, and analgesic activities, and is used as a complementary remedy to improve heart function and blood circulation. Since cardiovascular diseases are often associated with an alteration of mitochondria, the main producers of ATP in cardiac muscle cells, the aim of our work was to determine bioactive constituents present in motherwort aerial parts extract in ethanol and investigate their effects on the functions of cardiac mitochondria. Quantitative determination of polyphenols in L. cardiaca herb extract was performed by HPLC. Mitochondrial respiration rates were evaluated using a Clark-type oxygen electrode. Mitochondrial ROS generation was determined fluorimetrically with Amplex Red and horseradish peroxidase. The results showed that constituents (chlorogenic acid, orientin, quercetin, hyperoside, and rutin) of L. cardiaca herb extract uncouple (by 20-90 %) mitochondrial oxidation from phosphorylation, partially inhibit (by ~ 40 %) the mitochondrial respiratory chain in cases of pyruvate and malate as well as succinate oxidation, and effectively attenuate the generation of free radicals in mitochondria. Since partial uncoupling of mitochondria, respiratory inhibition, and decreased ROS production are proposed as possible mechanisms of cardioprotection, our results imply that L. cardiaca herb extract could be a useful remedy to protect cardiac muscles from the effects of pathogenic processes.

Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria.

Ursolic acid (1), a pentacyclic triterpene acid, is one of the major components of certain traditional medicinal plants and possesses a wide range of biological effects, such as anti-inflammatory, antioxidative, and cytotoxic activities. Furthermore, 1, when present at 1.6-5 ng/mL concentrations in commercial herbal preparations used for patients with cardiac disorders, may also exert pro-cardiac activities. There are several indirect suggestions that the cardioprotective mechanism of ursolic acid could involve the mitochondria; however the mechanism of action is still not known. Therefore, the effects of 0.4-200 ng/mL ursolic acid (1) on the functions of isolated rat heart mitochondria oxidizing either pyruvate and malate, succinate, or palmitoyl-l-carnitine plus malate were investigated. It was found that 1 induced a statistically significant uncoupling of oxidative phosphorylation. A statistically significant decrease in H2O2 production in the mitochondria was observed after incubation with 5 ng/mL 1. This effect was comparable to the effectiveness of the classical uncoupler carbonyl cyanide 3-chlorophenylhydrazone. Since mild mitochondrial uncoupling has been proposed as one of the mechanisms of cardioprotection, the present results indicate that ursolic acid (1) has potential use as a cardioprotective compound.

The coagulation system changes in patients with chronic heart failure.

Though heart failure can mainly be caused by systolic or diastolic dysfunction, the impairments of the neurohormonal, immune, and hemostatic systems are observed too. Therefore, it is not easy to determine etiology of the syndrome. Parameters that can be helpful to predict chronic heart failure, to evaluate its course and the risk of complications are still being searched. The aim of this article is to review the recent studies in order to find the links between the coagulation system and the development of chronic heart failure. Stress is a key factor for the development of most diseases including chronic heart failure too. Signals of emotional and physical stress via particular structures trigger an increase in concentrations of the following hormones: noradrenaline, renin, angiotensin II, aldosterone, vasopressin. It is proved that it causes the disorders of the coagulation system: an increase in the following factors of plasma coagulation (fibrinogen, VII, VIII, fibrinopeptide A, thrombin-antithrombin complex), fibrinolysis (D-dimer), endothelium (interleukin 1, endothelin 1, vascular cell adhesion molecules, endothelial growth factor), platelet activity (von Willebrand factor, intercellular adhesion molecules, platelet factor 4, P-selectin, thromboxane A(2), thromboglobulin, CD63P) and cytokines (tumor necrosis factor, interleukin 6) and decrease in E-selectin. The role of particular coagulation factors for the development of chronic heart failure has not been understood yet. Thus, it is necessary to carry out further studies.