Marian Valko

• Professor
• Senior Researcher at Slovak University of Technology in Bratislava

Heavy metals are naturally occurring components of the Earth’s crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting diffe...

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity...

Aging encompasses a wide array of detrimental effects that compromise physiological functions, elevate the risk of chronic diseases, and impair cognitive abilities. However, the precise underlying mechanisms, particularly the involvement of specific molecular regulatory proteins in the aging process, remain insufficiently understood. Emerging evide...

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-induci...

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer’s disease (AD) and Parkinson’s disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, thes...

The increasing pollution of ecosystems by both biological and non-biological contaminants has recently fostered the rapid development of biosensors, thus opening a new investigation area in analytical sciences. Here, we review the applications of immunosensors in food safety, human health, environmental sciences, water pollution, and agriculture. W...

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, car...

A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulati...

Phosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer...

Background and objectives Glioblastoma multiforme (GBM) is the most aggressive, malignant, and therapy-resistant tumor of the brain. Blockade therapy targeting the programmed cell death protein 1 (PD-1)/programmed death ligand (PD-L1) axis is currently under investigation for the clinical management of the GBM. This study has quantified the plasma...

Senescent cells persist and continuously secrete proinflammatory and tissue-remodeling molecules that poison surrounding cells, leading to various age-related diseases, including diabetes, atherosclerosis, and Alzheimer's disease. The underlying mechanism of cellular senescence has not yet been fully explored. Emerging evidence indicates that hypox...

Cellular senescence leads to decreased tissue regeneration and inflammation and is associated with diabetes, neurodegenerative diseases, and tumorigenesis. However, the mechanisms of cellular senescence are not fully understood. Emerging evidence has indicated that c-Jun N-terminal kinase (JNK) signaling is involved in the regulation of cellular se...

Cells produce reactive oxygen species (ROS) as a metabolic by-product. ROS molecules trigger oxidative stress as a feedback response that significantly initiates biological processes such as autophagy, apoptosis, and necrosis. Furthermore, extensive research has revealed that hydrogen peroxide (H 2 O 2) is an important ROS entity and plays a crucia...

Introduction: The objective of current project was to formulate a system for controlled delivery of Tramadol HCl (TRD), an opioid analgesic used in the treatment of moderate to severe pain. Methods: For this purpose, a pH responsive AvT-co-poly hydrogel network was formulated through free radical polymerization by incorporating natural polymers i.e...

In this work, attention is focused on the non-essential amino acid L-Tyrosine (TYR) hydroxylated to L-DOPA, which is the precursor to the neurotransmitters dopamine, noradrenaline (norepinephrine; NE) and adrenaline (epinephrine; EP) known as catecholamines and their interactions with redox-active Cu(II). Catecholamines have multiple functions in b...

The antioxidant properties of flavonoids are mediated by their functional hydroxyl groups, which are capable of both chelating redox active metals such as iron, copper and scavenging free radicals. In this paper, the antioxidant vs. prooxidant and DNA protecting properties of baicalein and Cu(II)-baicalein complexes were studied under the condition...

Herein, we discuss the synthesis, structural and spectroscopic characterization, and biological activity of five heteroligand copper(II) complexes with diethylnicotinamide and various fenamates, as follows: flufenamate (fluf), niflumate (nifl), tolfenamate (tolf), clonixinate (clon), mefenamate (mef) and N, N-diethylnicotinamide (dena). The complex...

The genetic variant A2 β-casein integrates the casein protein group in milk and has been often associated with positive health outcomes. Therefore, this review explores the present understanding of A2 β-casein, including detection methods and the market trends for dairy from A2 milk. Also, the interaction of A2 β-casein with αs1-casein and κ-casein...

Mycotoxins induce oxidative stress, hypoxia, and cause immunosuppressive effects. Moreover, emerging evidence show that mycotoxins have a potential of inducing cellular senescence, which are involved in their immunomodulatory effects. Mycotoxins upregulate the expression of senescence markers γ-H2AX, senescence-associated β-galactosidase, p53, p16,...

With approximately 1.8 million deaths in 2020, lung cancer remains the leading cause of cancer death globally, contributing 18% to the total cancer deaths. Various treatment choices are followed for lung cancer, including surgery, radiation therapy, chemotherapy and targeted therapy. Therapeutic modality recommendations rely on many factors, such a...

Medicinal plants have been exploited for therapeutic purposes since the dawn of civilization and have long been acknowledged essential to human health. The purpose of this research is to examine the scientific evidence for using the therapeutic herbal plants Thalictrum foliolosum DC. and Cordia dichotoma G. Forst. to treat hepatitis illness. The fu...

Cordia dichotoma, Indian cherry is one of the traditional medicinal plant well-known for its medicinal properties against variety of diseases primarily hepatocellular disorders. C. dichotoma is moderate size tree that may be found throughout the Himachal Pradesh and commonly called as lashuda. The objective of the present study is to emphasize the...

In total, twenty elements appear to be essential for the correct functioning of the human body, half of which are metals and half are non-metals. Among those metals that are currently considered to be essential for normal biological functioning are four main group elements, sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca), and six d-blo...

An innovative amperometric immunosensor has been developed to detect antibiotic colistin from the chicken liver. Colistin is a antibacterial peptide that has been barred for human consumption, but it is being commonly used as a veterinary drug, and as a feed additive for livestock. In the present work, an immunosensor was developed by immobilizing...

Aging is a progressive, unalterable physiological degradation process of living organisms, which leads to deterioration of biological function and eventually to senescence. The most prevalent factor responsible for aging is the accumulation of damages resulting from oxidative stress and dysbiosis. D-galactose-induced aging has become a hot topic, a...

Pine seeds are considered as nonwood forest products (NWFP) with regularly increasing market’s demand. They can be eaten in various ways such as roasted or raw. In addition, they are included in various traditional dishes like in cookies, sauces, candies, cakes, breads, and other bakery items and, moreover, for medicinal purposes. GC-MS study is pe...

Luteolin is a flavonoid possessing potential cardioprotective, anti-inflammatory, anti-cancer activities. Having multiple biological effects, luteolin may act as either an antioxidant or a pro-oxidant. In this work, the protective role of copper(II)-chelation by luteolin on DNA damage via the Cu-Fenton reaction was studied. EPR and UV–vis spectrosc...

Single crystals of 3,14-dimethyl-2,6,13,17-tetraazoniatricyclo(16.4.0.07,12)docosane tetrachloride tetrahydrate compound, [C20H44N4]Cl4·4H2O (1), were obtained by a novel synthetic route and characterized by elemental analysis and X-ray diffraction. The synthesized compound crystallized in the monoclinic space group P21/n with two molecules of comp...

An extensive characterization of [Ti(C22H18N2O6)]·H2O was performed by topological analysis according to Bader’s quantum theory of atoms in molecules (QTAIM) from the experimentally (multipole model) and theoretically (DFT) determined electron density. To the best of our knowledge, this study is the first example of an experimental electronic struc...

Kaempferol is a flavonoid that occurs in tea and in many vegetables and fruits, including broccoli, cabbage, beans, grapes, apples, and strawberries. The efficacy of Kaempferol has been demonstrated in the treatment of breast, esophageal, cervical, ovarian, and liver cancers and leukemia, which very likely arises from its prooxidant properties and...

Alzheimer's disease is a progressive brain disorder with characteristic symptoms and several pathological hallmarks. The concept of "one drug, one target" has not generated any new drugs since 2004. The new era of drug development in the field of AD builds upon rationally designed multi-target directed ligands that can better address the complexity...

Herein, two unsaturated macrocyclic copper(II) complexes, namely, [CuLA(ClO4)2] (1) [LA = 3,14-dimethyl-2,6,13,17-diazadiazoniatricyclo[16.4.0.07,12]docosa-2,13-diene) and [CuLB(ClO4)]ClO4 (2) (LB = 3,14-diethyl-2,6,13,17-diazadiazoniatricyclo[16.4.0.07,12]docosa-2,13-diene), were synthesized. The complexes were characterized by single-crystal X-ra...

Alzheimer’s disease (AD) is a complex disorder with unknown etiology. Currently, only symptomatic therapy of AD is available, comprising cholinesterase inhibitors and N-methyl-d-aspartate (NMDA) receptor antagonists. Drugs targeting only one pathological condition have generated only limited efficacy. Thus, combining two or more therapeutic interve...

Antimicrobial and antifungal activities of bifunctional copper(II) complexes with non-steroidal anti-inflammatory drugs, flufenamic, mefenamic and tolfenamic acids and 1,10-phenanthroline Abstract: Copper(II) complexes represent a promising group of compounds with antimicrobial and antifungal properties. In the present work, a series of Cu(II) comp...

Computer-aided drug design (CADD) methodologies are playing an ever-increasing role in drug discovery that are critical in the cost-effective identification of promising drug candidates. These computational methods are relevant in limiting the use of animal models in pharmacological research, for aiding the rational design of novel and safe drug ca...

Computer-aided drug design (CADD) methodologies are playing an ever increasing role in drug discovery that and are critical in the cost effective identification of promising drug candidates. These computational methods are relevant for limiting the use of animal models in pharmacological research, for aiding the rational design of novel and safe dr...

A novel oxalato-bridged trinuclear heterometallic complex, cis-[Cr(cyc b)(μ-1,2,3,4-ox)ZnCl2(μ-1,2,3-ox)Cr(cyc b)]ZnCl4·H2O (1) (cyc b = rac-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; C16H36N4, ox = oxalate; C2O4²⁻), was prepared and its structure was determined by single-crystal X-ray diffraction analysis at 100 K. Complex 1 crys...

The antioxidant and/or prooxidant properties of flavonoids are strongly dependent on their redox metal chelating capacity as well as on the number and positions of hydroxyl groups. In this work the interaction between Cu(II) ion and the set consisting of four flavonoids (myricetin, morin, taxifolin and 3′,4′-dihydroxyflavone) is investigated using...

Reactions of non-steroidal anti-inflammatory drugs tolfenamic (Htolf), meclofenamic (Hmeclf), mefenamic (Hmef), clonixic (Hclon) and niflumic (Hnif) acids with isonicotinamide (isn) and copper(II) acetate resulted in formation of five novel mixed-ligands Cu(II) coordination compounds: [Cu(tolf-O,O')2(isn-N)2] (1), [Cu(meclf-O,O')2(isn-N)2] (2), [Cu...

The beneficial effects of polyphenols, predominantly in the context of oxidative stress-related diseases such as cancer, cardiovascular diseases and neurological conditions including Alzheimer’s and Parkinson’s diseases, have been documented by a number of papers and reviews. The antioxidant/prooxidant properties of phenolic compounds are related m...

In this study, two Cu²⁺-doped single crystals, [Cu0.02(H1.96L)](ClO4)2 (1) and [Cu0.91(H0.18L)](ClO4)2 (2) (L = 3,14-diethyl-2,6,13,17-tetraazatricyclo(16.4.0.07,12)docosane), were prepared and characterized by elemental and X-ray crystal structural analyses, along with UV–visible, infrared (IR) and electron paramagnetic resonance (EPR) spectroscop...

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder, characterized by the formation, aggregation and accumulation of amyloid beta, perturbed metal (copper, iron and zinc) homeostasis, metal-induced oxidative stress, neuroinflammation, aberrant activity of acetylcholinesterase (AChE) and other pathologies. The aim of this review...

A newly prepared Cu(II) complex salt, Cu(L1)(H2O)2Br2, where L1 is 3,14-dimethyl-2,6,13,17-tetraazatricyclo(16.4.0.07,12) docosane, is characterized by elemental and crystallographic analyses. The Cu(II) center is coordinated by four nitrogen atoms of macrocyclic ligand and the axial position by two water molecules. The macrocyclic ligand adopts an...

Cyclam derivatives and their metal complexes have been found to exhibit an anti-HIV effect and stimulate the activity of stem cells from bone marrow. The strength of their binding to the CXCR4 receptor correlates with anti-HIV and stem-cell activities. Knowledge of the conformation and crystal packing of various macrocyclic metal complexes has beco...

Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are therefore highly toxic compounds. For the recovery of inhibited AChE, antidotes from the group of pyridinium or bispy...

Nicotinamide has been employed as a supramolecular reagent in the synthesis of ten copper(II) chloro-, bromo-, fluoro-, iodo-, and dichlorobenzoate complexes. Compound structures were determined by single-crystal X-ray diffraction structural analysis. All ten compounds are monomeric complexes with a square-bipyramidal coordination sphere around the...

The radical scavenging and metal chelating properties of flavonoids indicate that they may play a protective role in diseases with perturbed metal homeostasis such as Alzheimer's disease. In this work we investigated the effect of the coordination of quercetin to copper(II) in view of the formation of ROS in Cu-catalyzed Fenton reaction. ABTS and D...

The synthesis and characterization of [Cu(5-Me-2-tpc)2(4-pyme)2] (I), [Cu(3-Me-2-tpc)2(4-pyme)2] (II), [Cu(2-tpc)2(4-pyme)2] (III), [Cu(2-tpc)2(isonia)2(2-tpcH)] (IV), [Cu(5-Me-2-tpc)2(isonia)2(5-Me-2-tpcH)] (V), [Cu2(2-tpc)4(4-pyme)2] (VI), [Cu2(3-Me-2-tpc)4(isonia)2] (VII) (where 2-tpc is 2-thiophenecarboxylate, 3-Me-2-tpc is 3-methyl-2-thiophene...

The influence of the hydration and drying process on the line shape and signal intensity of the electron paramagnetic resonance spectra recorded from Cu(II) ions present in silica xerogels calcined at various temperatures was investigated. The experimental Cu(II) electron paramagnetic resonance spectra were found to consist of a superimposition of...

Cancer and Alzheimer’s disease (AD) are characterized by (i) opposing biological mechanisms, (ii) an inverse correlation between their incidences, and (iii) oxidative stress being a common denominator of both diseases. Increased formation of reactive oxygen species (ROS) in cancer cells from oncogenic signaling and/or metabolic disturbances leads t...

Medicinal plants are a significant source of biological active and health protective compounds. Post-harvest treatments can affect, in different ways, the content and biological activity of such compounds. One of the most common post-harvesting methods is drying. In this study, we investigated the effect of drying method on the content of natural p...

Free radicals are species containing one or more unpaired electrons. Unpaired or free electrons are responsible for enhanced reactivity of free radicals with various biomolecules. Most frequently occurring radicals in biological systems are reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS are generated by the tightly r...

Purpose of Review Chelation therapy is used for diseases causing an imbalance of iron levels (for example haemochromatosis and thalassaemia) or copper levels (for example Menkes’ and Wilson’s diseases). Currently, most pharmaceutical chelators are relatively simple but often have side effects. Some have been taken off the market. This review attemp...

Transition metal ions are key elements of various biological processes ranging from oxygen formation to hypoxia sensing, and therefore, their homeostasis is maintained within strict limits through tightly regulated mechanisms of uptake, storage and secretion. The breakdown of metal ion homeostasis can lead to an uncontrolled formation of reactive o...

The various stages of the tetraethyl orthosilicate-based sol–gel process were studied using Gd(III) cations as a spin probe, using EPR spectroscopy at ambient and liquid nitrogen temperatures. The Gd(III) EPR spectra (being of the ‘U-spectrum’ type) were very similar, as recorded at 77 K, at the various defined stages of the sol–gel process. The an...

The various stages of the tetraethyl orthosilicate-based sol–gel process were investigated using electron paramagnetic resonance (EPR) spectroscopy with Cu(II) cations as a spin probe. The latter were introduced to the starting reaction mixture in the form of various copper(II) salts containing anions of different basicity (CuCl2, Cu(ac)2, or CuSO4...

Nicotinamide was employed as a supramolecular reagent in the synthesis of six new copper(II) bromo-, iodo-, fluoro- and dibromobenzoate complexes. Structures of [Cu(2-Brbz)2(nia)2(H2O)2] (I ), [Cu(2-Ibz)2(nia)2(H2O)2] (II ), [Cu(2-Fbz)2(nia)2(H2O)2] (III ), [Cu(4-Brbz)2(nia)2(H2O)2] (IV ), [Cu(3,5-Br2bz)2(nia)2(H2O)2] (V), [Cu(F-Fbz)2(nia)2(H2O)] ·...

The synthesis, crystal structures and spectroscopy of [{Cu(μ2-adip)(benzim)2(H2O)}n] (1), [{Cu(μ2-adip)(4-pyme)2(H2O)}n] (2), [{Cu(μ3-adip)(nia)2}n·nH2O] (3), [{Cu(μ2-adip)(pydca)2}n] (4) and [{Cu(μ4-adip)(mna)}n·nH2O] (5) (adip = adipate2- anion, benzim = benzimidazole, 4-pyme = 4-pyridylmethanol, nia = nicotinamide, pydca = 3,4-pyridinedicarboxam...

The various stages of the TEOS-based sol–gel process were studied by EPR spectroscopy using a VO(II) spin-probe. A detailed analysis of the multicomponent VO(II) EPR spectra recorded at 77 K showed that three main types of individual signals appeared superimposed at the various stages of the sol–gel process, which corresponds to different environme...

The presented paper is focused on the calculation of hyperfine coupling constants (HFCC) of Cu 2+ ion in water environment. To simulate the conditions of the electron paramagnetic resonance (EPR) experiment in aqueous phase, molecular dynamics using the density functional theory (DFT) was employed. In total three different functionals (BLYP, B3LYP,...

Mixed ligand copper(II) complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II) complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo) and salicylate ligands (Sal) are...

Irinotecan (CPT-11) is an efficient anticancer drug approved for clinical use in the treatment of advanced colorectal cancers. This work is focused on the study of photoinduced processes in irinotecan (CPT-11) both in the presence and absence of Cu(II) ions by means of UV/vis and EPR spectroscopy. Solid-state EPR revealed the solvent dependent coor...

Redox active transition metal ions (e.g., iron and copper) have been implicated in the etiology of many oxidative stress-related diseases including also neurodegenerative disorders. Unbound copper can catalyze formation of reactive oxygen species (hydroxyl radicals) via Fenton reaction/Haber–Weiss chemistry and therefore, under physiological condit...

Carotenoids are natural pigments attracting attention of physicists, chemists and biologists due to their multiple functions in the nature. While carotenoids have unusually high extinction coefficients, they do not exhibit adequate emission. This fact has resulted in detailed studies of photophysical and photochemical properties of carotenoids and...

Copper(II) complex systems, containing 3,5-dichlorosalicylic acid (3,5-Cl2salH) and different copper salts (Cu(ac)2 or CuSO4), with varying concentrations of 3-pyridylmethanol (ronicol, ron) or N,N′-diethylnicotinamide (denia) as ligands, were prepared. The effects of Cu(II) salts containing anions of different basicity and two different N-donor li...

Copper(II) complexes, formed from 4-chlorosalicylic acid anion A (A = 4-Clsal-), different copper(II) salts (Cu(ac)2 or CuSO4) and different N-donor ligands B (B = 3-pyridylmethanol (ron) or N,N'-diethylnicotinamide (denia)) with varying N-donor ligand-to-metal ratio (x), were studied by EPR spectroscopy in the frozen water/methanol (1:3 v/v) solut...

Copper(II) complex systems containing 3,5-di, 4-, or 5-chlorosalicylic acids (X-ClsalH) and different copper(II) salts (copper acetate (Cu(ac)2) or copper sulphate (CuSO4)), with varying 2,6-pyridinedimethanol (pydime) concentration, [Cu(ac)2(aq) or CuSO4(aq) + 2 (X-ClsalH(solv)) + x pydime(solv)], where X = 3,5-di, 4-, or 5- and x = 0, 1, 2, 4, or...

SynonymsChelation therapy; Inorganic mercury; Mercury poisoning; Mercury-induced oxidative stress; Organic mercuryDefinitionMercury is the 80th element on the periodic table and is unique in that it is found in nature in several chemical and physical forms (Stohs and Bagchi 1995; Valko et al. 2005). Hg is a heavy metal and exists as several species...

New coordination polymers based on copper(II) benzoate and pyridinecarboxylate compounds bridged by 3-pyridylmethanol, [CuX2(l-3PM)2]n (where X = 2-methyltionicotinate (2-MeSnic) or 2-chlorobenzooate (2-Clbz) and [Cu3(2-Clnic)6(l-3PM)4(3PM)2]n (2-Clnic = 2-chloronicotinate) have been prepared and spectroscopically studied. Both the [CuX2(3PM)2]n co...

The structure and properties of the glass products prepared by the sol-gel process are strongly dependent on the experimental conditions of their preparation. The time dependence of the structural intermediate formation obtained during hydrolysis and condensation reactions in tetraethoxysilane, ethanol, H2O, HCl (molar ratio 1:3:1.5:0.01) sol-gel r...

A number of studies performed on biological systems have shown that redox-active metals such as iron and copper as well as other transition metals can undergo redox cycling reactions and produce reactive free radicals termed also reactive oxygen species (ROS) or reactive nitrogen species (RNS). The most representative examples of ROS and RNS are th...

This contribution reports on the thermodynamics of free radical reactions and the maintenance of cell redox homeostasis. Attention is focused on the definition of the half-cell reduction potential and the reducing capacity of the antioxidant couples, the cellular defence system substantiated by the thioredoxin, NADP(H), ascorbic acid, and thiol-con...

Introduction Reduction, Oxidation, and the Thermodynamics of Free Radical Reactions Oxidative Stress and Redox Environment of a Cell ROS, Signal Transduction, and Human Disease Diabetes Neurological Disorders Conclusion Acknowledgments References

Iron is a redox active metal involved in the oxidation-reduction reactions and regulation of cell growth and differentiation. Iron is an integral part of many proteins and enzymes that maintains various physiological functions. Most of the human body's iron is contained in red blood cells. Despite iron being an abundant trace metal in food, million...

The title compound, [Cu4(C7H4ClO2)4(C6H6NO)4], consists of isolated tetra­nuclear clusters, where the Cu²⁺ cations are five- and sixfold coordinated by O atoms from the 4-chloro­benzoate anions and by pyridine N and methanol­ate O atoms from bidentate 2-pyridylmethanolate ligands. While three Cu atoms are six-coordinated by an NO5 donor set forming...