Joanna Kocot

The many “faces” of copper in medicine and treatment

Copper (Cu) is an essential microelement found in all living organisms with the unique ability to adopt two different redox states—in the oxidized (Cu2+) and reduced (Cu+). It is required for survival and serves as an important catalytic cofactor in redox chemistry for proteins that carry out fundamental biological functions, important in growth and development. The deficit of copper can result in impaired energy production, abnormal glucose and cholesterol metabolism, increased oxidative damage, increased tissue iron (Fe) accrual, altered structure and function of circulating blood and immune cells, abnormal neuropeptides synthesis and processing, aberrant cardiac electrophysiology, impaired myocardial contractility, and persistent effects on the neurobehavioral and the immune system. Increased copper level has been found in several disorders like e.g.: Wilson’s disease or Menke’s disease. New findings with the great potential for impact in medicine include the use of copper-lowering therapy for antiangiogenesis, antifibrotic and anti-inflammatory purposes. The role of copper in formation of amyloid plaques in Alzheimer’s disease, and successful treatment of this disorder in rodent model by copper chelating are also of interest. In this work we will try to describe essential aspects of copper in chosen diseases. We will represent the evidence available on adverse effect derived from copper deficiency and copper excess. We will try to review also the copper biomarkers (chosen enzymes) that help reflect the level of copper in the body.

Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders

Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders.

Effect of sodium selenite on chosen anti- and pro-oxidative parameters in rats treated with lithium: A pilot study

BACKGROUND Selenium is an essential element of antioxidant properties. Lithium is widely used in medicine but its administration can cause numerous side effects including oxidative stress. The present study aimed at evaluating if sodium selenite could influence chosen anti- and pro-oxidant parameters in rats treated with lithium. METHODS The experiment was performed on four groups of Wistar rats: I (control) - treated with saline; II (Li) - treated with lithium (2.7 mgLi/kg b.w. as Li2CO3), III (Se) - treated with selenium (0.5 mgSe/kg b.w. as Na2SeO3), IV (Li+Se) - treated with Li2CO3 and Na2SeO3 together at the same doses as in group II and III, respectively. All treatments were performed by stomach tube for three weeks in form of water solutions. The following anti- and pro-oxidant parameters: total antioxidant status (TAS) value, catalase (CAT) activity, concentrations of ascorbic acid (AA) and malonyldialdehyde (MDA) in plasma as well as whole blood superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured. RESULTS Selenium given alone markedly enhanced whole blood GPx and diminished plasma CAT vs. CONTROL Lithium significantly decreased plasma CAT and slightly increased AA vs. CONTROL Selenium co-administration restored these parameters to the values observed in control animals. Furthermore, selenium co-administration significantly increased GPx in Li-treated rats. All other parameters (TAS, SOD and MDA) were not affected by lithium and/or selenium. CONCLUSION Further research seems to be warranted to decide if application of selenium as an adjuvant in lithium therapy is worth considering.

Selenium – a fascinating antioxidant of protective properties

Selenium is a trace element which fulfils important functions in the organism. Its deficit may cause acute disorders, but an overdose can also lead to severe consequences. The functions of selenium in the organism are mainly connected with its antioxidant properties, as it is an essential part of important antioxidant enzymes. Disturbances of oxidant balance have been found to be involved in the activity of numerous harmful factors as well as in the pathogenesis of diverse illnesses. Selenium administration has proved to be effective against the toxicity of many agents and the side effects of drugs. However, the narrow range between therapeutic and toxic doses of selenium, as well as the dependence of its effect on the applied form, dose and method of treatment, makes the choice of the most effective supplement a very complex issue. Divergent forms of selenium are still being studied, including both inorganic and organic compounds as well as Se-enriched natural products. The newest research has also involved selenium nanoparticles. The aim of this review is to present the great potential of selenium for protecting the organism against a wide variety of environmental pollutants, drugs and physical factors.

The investigation of the possible protective influence of selenium on antioxidant barrier in heart of rats exposed to lithium.

AIMS Selenium is an essential element possessing antioxidant properties and the treatment with it has displayed protective effects against toxicity of different substances occurring in the environment and food as well as against the side effects of some drugs. Lithium is used in medicine although numerous side effects can occur during therapy, including disturbances of the heart. For these reasons studies to find protective adjuvants have been performed. In the current study the possibility of selenium (as sodium selenite) application as a protective adjuvant in lithium treatment was studied. MAIN METHODS Male Wistar rats were treated: control - with saline; Li-group - with Li2CO3 (2.7 mg Li/kg b.w.); Se-group - with Na2SeO3 (0.5 mg Se/kg b.w.); Li+Se-group simultaneously with Li2CO3 and Na2SeO3 (2.7 mg Li/kg b.w. and 0.5 mg Se/kg b.w., respectively) by a stomach tube for a period of three weeks, once a day. In heart homogenate activities of antioxidant enzymes - catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx), concentrations of low-molecular-weight antioxidants - ascorbic acid (AA) and reduced glutathione (GSH) as well as total antioxidant status (TAS) values were determined. GPx/SOD and CAT/SOD ratios were evaluated. KEY FINDINGS In comparison with control selenium caused no significant changes of the studied parameters except for GPx, whereas lithium slightly disturbed TAS and markedly GPx, CAT and CAT/SOD ratio. In Li-treated rats co-administration of selenium displayed tendency towards restoring the impaired parameters. SIGNIFICANCE The results suggest that research on selenium application as an adjuvant in lithium therapy is worthy to be continued.

Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity

Background The fast pace of life, promoting fast food consumption and low physical activity, has resulted in obesity and/or diabetes as being serious social problems. The aim of the present study was to evaluate concentrations of selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in relation to degree of obesity. Material/Methods The study comprised 92 T2D subjects divided into 4 groups according to BMI value – I (normal body weight), II (overweight), III (obesity), and IV (severe obesity) – and 20 healthy volunteers (control group). Each group was divided into male and female subgroups. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. Results In women, leptin concentration was significantly higher in group IV, whereas in men it was higher in groups III and IV than in the control group and groups I and II. Irrespective of sex, a significant decrease in adiponectin level was observed in group III vs. control. There was no significant difference in resistin levels. In women visfatin was markedly enhanced in group III, whereas in men in groups II, III and IV vs. control. Leptin/adiponectin ratio was increased in groups III and IV vs. control in women, whereas in men vs. both control and group I. Conclusions The obese type 2 diabetic patients presented a disturbed adipokine profile, which seems to be an important link between obesity and T2D. The future studies concerning the question if regulating of adipokines’ concentrations could be a promising approach for managing metabolic disorders seem to be well-grounded.

Comparison of the influence of selenium supplementation in organic and inorganic forms on oxidant/antioxidant balance in rat lungs

Abstract The aim of the experiment was to compare the effect of two newly synthesised organic selenocompounds with that exerted by sodium selenite on oxidant processes in rat lungs. Total antioxidant status (TAS), activity of antioxidant enzymes - superoxide dismutase (SOD) and glutathione peroxidase (GPx), concentrations of non-enzymatic antioxidants - ascorbic acid (AA) and reduced glutathione (GSH), concentration of lipid peroxidation marker - malonyldialdehyde (MDA), as well as tissue concentrations of silicon and magnesium were determined in rats receiving different selenocompounds (inorganic selenite and organic selenosemicarbazide in a chain form - compound A and selenazoline in a ring form - compound B). TAS values were elevated in comparison with control without Se-supplementation. GPx was insignificantly increased when compared to control, mainly in the group receiving compound B. Inorganic selenite significantly increased SOD and decreased levels of AA. MDA was slightly altered in Se-supplemented animals. Silicon levels were not affected, whereas magnesium concentrations were considerably reduced in all groups receiving selenium. Compound B increased TAS to the highest degree. It did not have any impact on components of the antioxidant barrier and slightly decreased MDA. Therefore, it could be suggested that further research, including in vitro studies on cancer cell lines, may reveal new possibilities of medical applications of selenocompounds

Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application

Honeybees products comprise of numerous substances, including propolis, bee pollen, and royal jelly, which have long been known for their medicinal and health-promoting properties. Their wide biological effects have been known and used since antiquity. Bee products are considered to be a potential source of natural antioxidants such as flavonoids, phenolic acids, or terpenoids. Nowadays, the still growing concern in natural substances capable of counteracting the effects of oxidative stress underlying the pathogenesis of numerous diseases, such as neurodegenerative disorders, cancer, diabetes, and atherosclerosis, as well as negative effects of different harmful factors and drugs, is being observed. Having regarded the importance of acquiring drugs from natural sources, this review is aimed at updating the current state of knowledge of antioxidant capacity of selected bee products, namely, propolis, bee pollen, and royal jelly, and of their potential antioxidant-related therapeutic applications. Moreover, the particular attention has been attributed to the understanding of the mechanisms underlying antioxidant properties of bee products. The influence of bee species, plant origin, geographic location, and seasonality as well as type of extraction solutions on the composition of bee products extracts were also discussed.

Different patterns of gelatinolytic activity in pituitary macro- and microadenomas

OBJECTIVE Gelatinases, Matrix MetalloProteinase(MMP)-2 and MMP-9, belong to zinc-dependent endopeptidases involved in several physiological and pathological processes including inflammation and tumor development. Because the information about the involvement of gelatinases in pituitary adenoma (PA) development are scant, our objective was the analysis of MMP-2 and MMP-9 activity in serum and tumor tissue of PA patients. PATIENTS AND METHODS Twenty one patients with PA (macroadenoma n=18, microadenoma n=3), qualified to the endoscopic resection of tumors were enrolled. Venous blood samples were collected before the surgery and PA tissue was collected during the surgery. Tissue material was homogenized in a buffer containing 0.1M Tris-HCl pH 7.4 and centrifuged. The supernatant was set to the equal protein content 18μg/sample. Protein level in tissue samples was estimated with Bradford method. MMP-2 and MMP-9 analysis in serum and tissue was performed with gelatin zymography. RESULTS The proteolytically activated forms of MMPs were not observed in the analyzed sera. Serum activities of MMP-2 and MMP-9 did not statistically differ between patients with micro and macroadenomas. The analysis of material obtained from tissue of microadenomas showed slightly lower activities of both forms of MMP-9 (pro-MMP-9 and MMP-9/lipokalin heterodimer). Simultaneously the increased activity of pro-MMP-2 in comparison to macroadenomas was observed. Although differences observed did not reach statistical significance, only in the case of microadenomas the presence of the active form of MMP-2 (molecular weight 65kDa band) was observed. CONCLUSION In the course of PA growth the change the biochemical profile of the gelatinolytic activity within the tumor tissue is observed. Initially, the higher activity of MMP-2 in microadenomas and elevated activity of MMP-9 in macroadenomas were detected.

Is There Any Relationship between Plasma 25-Hydroxyvitamin D3, Adipokine Profiles and Excessive Body Weight in Type 2 Diabetic Patients?

A growing interest in the role of vitamin D in metabolic diseases led us to study the relationships between 25-hydroxyvitamin D3 (25(OH)D3) and the profiles of selected adipokines in type 2 diabetic (T2DM) patients. The study comprised 92 type 2 diabetics divided into quartiles regarding 25(OH)D3 concentration. Each group was divided into male and female subgroups. All the studied patients had their anthropometric and biochemical parameters determined. Plasma 25-hydroxyvitamin D3 concentration was determined by HPLC, while the selected adipokines (leptin, adiponectin, resistin and visfatin) by ELISA methods. The ratio of leptin to adiponectin (L/A) was calculated for all the patients. In 85.3% of diabetics a full (<20 ng/mL) or moderate (20–30 ng/mL) vitamin D deficit was found. Irrespective of sex, plasma leptin concentration decreased across increasing quartiles of 25(OH)D3 level. In women, 25(OH)D3 was negatively correlated with BMI, leptin level as well as L/A ratio, and positively with adiponectin concentration. In men, 25(OH)D3 was positively correlated with HDL and negatively with systolic blood pressure (SBP), leptin level and L/A ratio. Considering all the patients, there ocurred a significant negative correlation between 25(OH)D3 and SBP, BMI, WHR, TG, leptin and L/A ratio and positive ones between 25(OH)D3 and both adiponectin and HDL. The results of the study support the existence of the relationship among vitamin D, obesity and leptin in type 2 diabetic patients.