Human Blood Plasma Proteins Research Articles

Production of Recombinant Polypeptides Binding α2-Macroglobulin and Analysis of Their Ability to Bind Human Serum α2-Macroglobulin.

Many streptococcal strains bind to two main human blood plasma proteins: IgG and human serum albumin (HSA). Protein G expressed in group C and G streptococci has specific binding regions for these proteins. Protein G in group G streptococcal strains also contains a region binding another human plasma protein, α2-macroglobulin (α2-М), upstream to the HSA-binding domain. Two recombinant polypeptides GM and GM1 capable of binding to α2-М were obtained using the G4223 strain of a group G Streptococcus, protein G molecule of which interacts with three human blood serum proteins (IgG, HSA, and α2-М). However, polypeptide GM containing three IgG-binding and three HSA-bindings domains and the region binding α2-М has higher molecular mass and higher affinity to α2-М than polypeptide GM1 that includes only the α2-М binding region.

Molecular Mechanisms of the Interactions of N-(2-Hydroxypropyl)methacrylamide Copolymers Designed for Cancer Therapy with Blood Plasma Proteins.

The binding of plasma proteins to a drug carrier alters the circulation of nanoparticles (NPs) in the bloodstream, and, as a consequence, the anticancer efficiency of the entire nanoparticle drug delivery system. We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (pHPMA) with the most abundant proteins in human blood plasma—namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1—using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR). Through rigorous investigation, we present evidence of weak interactions between proteins and polymeric nanomedicine. Such interactions do not result in the formation of the protein corona and do not affect the efficiency of the drug delivery.

UV-photofunctionalization of a biomimetic coating for dental implants application.

Photofunctionalization mediated by ultraviolet (UV) rays changes the physico-chemical characteristics of titanium (Ti) and improves the biological activity of dental implants. However, the role of UV-mediated photofunctionalization of biofunctional Ti surfaces on the antimicrobial and photocatalytic activity remains unknown and was investigated in this study. Commercially pure titanium (cpTi) discs were divided into four groups: (1) machined samples without UV light application [cpTi UV-]; (2) plasma electrolytic oxidation (PEO) treated samples without UV light application [PEO UV-]; (3) machined samples with UV light application [cpTi UV+]; and (4) PEO-treated samples with UV light application [PEO UV+]. The surfaces were characterized according to their morphology, roughness, crystalline phase, chemical composition and wettability. The photocatalytic activity and proteins adsorption were measured. For the microbiological assay, Streptococcus sanguinis was grown on the disc surfaces for 1h and 6h, and the colony forming units and bacterial organization were evaluated. In addition, to confirm the non-cytotoxic effect of PEO UV +, human gingival fibroblast (HGF) cells were cultured in a monolayer onto each material surface and the cells viability and proliferation evaluated by a fluorescent cell staining method. PEO treatment increased the Ti surface roughness and wettability (p<0.05). Photofunctionalization reduced the hydrocarbon concentration and enhanced human blood plasma proteins and albumin adsorption mainly for the PEO-treated surface (p<0.05). PEO UV+ also maintained higher wettability values for a longer period and provided microbial reduction at 1h of bacterial adhesion (p=0.012 vs. PEO UV-). Photofunctionalization did not increase the photocatalytic activity of Ti (p>0.05). Confocal microscopy analyses demonstrated that PEO UV+ had no cell damage effect on HGF cells growth even after 24h of incubation. The photofunctionalization of a biofunctional PEO coating seems to be a promising alternative for dental implants as it increases blood plasma proteins adsorption, reduces initial bacterial adhesion and presents no cytotoxicity effect.

Cadmium-binding proteins in human blood plasma

Blood is the transmission medium for metal contaminants to and from bodily organs; as such, it can provide useful and reliable information about their bio-kinetics as they're distributed throughout the body. Metals can interact with endogenous proteins present in the blood, and these metal-protein complexes often dictate the fates of the introduced metals. The aim of this study was to investigate cadmium-binding protein characteristics in normal human plasma. Cadmium-binding plasma proteins in two different groups: normal human plasma (n = 29), and normal paired maternal and fetal umbilical cord plasmas (n = 3), were analyzed. In order to detect cadmium-binding plasma proteins present in low concentrations, blood plasma samples were first depleted of their two most abundant proteins - albumin and immunoglobulin G. Both the crude and depleted plasma samples were analyzed using column gel electrophoresis in conjunction with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). One cadmium-binding protein was detected in 11 of 29 normal plasma samples and all three paired maternal and cord plasma samples. This protein was further identified as apolipoprotein A-I by high-resolution mass spectrometry. To the best of our knowledge, this is the first study to reveal cadmium-binding proteins in real human blood plasma, which is extremely critical to our understanding of cadmium transportation and accumulation in human blood.

A multiscale model of protein adsorption on a nanoparticle surface

We present a methodology to quantify the essential interactions at the interface between inorganic solid nanoparticles (NPs) and biological molecules. Our model is based on pre-calculation of the repetitive contributions to the interaction from molecular segments, which allows us to efficiently scan a multitude of molecules and rank them by their adsorption affinity. The interaction between the biomolecular fragments and the nanomaterial are evaluated using a systematic coarse-graining scheme starting from all-atom molecular dynamics simulations. The NPs are modelled using a two-layer representation, where the outer layer is parameterized at the atomistic level and the core is treated at the continuum level using Lifshitz theory of dispersion forces. We demonstrate that the scheme reproduces the experimentally observed features of the NP protein coronas. To illustrate the use of the methodology, we compute the adsorption energies for human blood plasma proteins on gold NPs of different sizes as well as the preferred orientation of the molecules upon adsorption. The computed energies can be used for predicting the composition of the NP-protein corona for the corresponding material.

Investigation of relaxation times in 5-fluorouracil and human serum albumin mixtures

Abstract Background Human serum albumin (HSA) is often selected as a subject of any study because albumin is the most abundant protein in human blood plasma. NMR is recognized as a valuable method to determine the structure of proteins-ligand and protein-drug complexes. Objective – Aim of the study In this study, protein drug interactions were investigated using 5-Fluorouracil anti-cancer drug and human serum albumin protein. Materials and methods In this context 400 MHz NMR spectrometry was used and NMR relaxation rates in drug-albumin complex were investigated with respect to increase albumin concentration and increase in 5-Fluorouracil (5-FU)-albumin solution temperature. Results The results of this study indicated that 5-FU had a weak association with albumin, and it easily dissociated from the protein to which it was attached. Conclusion The obtained results also gave us useful information about molecular dynamics of drug-albumin interactions.

Nano- and Micropatterned Polycaprolactone Cellulose Composite Surfaces with Tunable Protein Adsorption, Fibrin Clot Formation, and Endothelial Cellular Response.

This work describes the interaction of the human blood plasma proteins albumin, fibrinogen, and γ-globulins with micro- and nanopatterned polymer interfaces. Protein adsorption studies were correlated with the fibrin clotting time of human blood plasma and with the growth of primary human pulmonary artery endothelial cells (hECs) on these patterns. It was observed that blends of polycaprolactone (PCL) and trimethylsilyl-protected cellulose form various thin-film patterns during spin coating, depending on the mass ratio of the polymers in the spinning solutions. Vapor-phase acid-catalyzed deprotection preserves these patterns but yields interfaces that are composed of hydrophilic cellulose domains enclosed by hydrophobic PCL. The blood plasma proteins are repelled by the cellulose domains, allowing for a suggested selective protein deposition on the PCL domains. An inverse proportional correlation is observed between the amount of cellulose present in the films and the mass of irreversibly adsorbed proteins. This results in significantly increased fibrin clotting times and lower masses of deposited clots on cellulose-containing films as revealed by quartz crystal microbalance with dissipation measurements. Cell viability of hECs grown on these surfaces was directly correlated with higher protein adsorption and faster clot formation. The results show that presented patterned polymer composite surfaces allow for a controllable blood plasma protein coagulation and a significant biological response from hECs. It is proposed that this knowledge can be utilized in regenerative medicine, cell cultures, and artificial vascular grafts by a careful choice of polymers and patterns.

Using Neuroscience, Contemporary methods and Traditional Wisdom in Building Well-being in Long Term Unemployed Youth

Advanced glycation end-products (AGEs) from non-enzymatic glycation are implicated in several degenerative diseases, including being a crucial contributor in secondary complications of diabetes. This has garnered significant scientific interest in inhibiting agents of AGEs to prevent and remediate disorders arising due to glycation. In the current study, inhibitory effects on AGEs formation were investigated using bio-enzymatically synthesized nanoformulations of gold (AuNPs) and silver (AgNPs) by physiologically important enzyme, β galactosidase. Human serum albumin, most abundant protein in human blood plasma, was glycated by incubating with glucose leading to AGEs formation. The AGEs formation was significantly minimized with both AuNPs and AgNPs, as confirmed by various biophysical and biochemical techniques. Circular dichroism and Fourier transform infrared spectroscopy further affirmed antiglycation potential of AuNPs and AgNPs. The results were corroborated with thiol group, free lysine and carbonyl content estimation for native, glycated and nanoparticles (NPs) treated samples. Confocal microscopic imaging was performed to exhibit glycation inhibiting potential of the NPs. The inhibition of AGEs was observed to be slightly stronger in case of AgNPs than AuNPs with both exhibiting promising results as potential anti-glycating agents. The study sheds light on potential of non-toxic NPs being utilized as controlling agents against hyperglycemic conditions and diabetes management.

Suppression in advanced glycation adducts of human serum albumin by bio-enzymatically synthesized gold and silver nanoformulations: A potential tool to counteract hyperglycemic condition

Advanced glycation end-products (AGEs) from non-enzymatic glycation are implicated in several degenerative diseases, including being a crucial contributor in secondary complications of diabetes. This has garnered significant scientific interest in inhibiting agents of AGEs to prevent and remediate disorders arising due to glycation. In the current study, inhibitory effects on AGEs formation were investigated using bio-enzymatically synthesized nanoformulations of gold (AuNPs) and silver (AgNPs) by physiologically important enzyme, β galactosidase. Human serum albumin, most abundant protein in human blood plasma, was glycated by incubating with glucose leading to AGEs formation. The AGEs formation was significantly minimized with both AuNPs and AgNPs, as confirmed by various biophysical and biochemical techniques. Circular dichroism and Fourier transform infrared spectroscopy further affirmed antiglycation potential of AuNPs and AgNPs. The results were corroborated with thiol group, free lysine and carbonyl content estimation for native, glycated and nanoparticles (NPs) treated samples. Confocal microscopic imaging was performed to exhibit glycation inhibiting potential of the NPs. The inhibition of AGEs was observed to be slightly stronger in case of AgNPs than AuNPs with both exhibiting promising results as potential anti-glycating agents. The study sheds light on potential of non-toxic NPs being utilized as controlling agents against hyperglycemic conditions and diabetes management.

Investigation of changes in the expression of human blood plasma proteins in major depressive disorder patients associated to an effective antidepressant response

Major depressive disorder is a complex multi-factor psychiatric disorder whose consequences can be debilitating, being one of the main worldwide causes of suicide. Its treatment is predominantly antidepressants and regular counseling and despite the treatment’s effectiveness, 10-30% of the patients respond differently and present adverse reactions to it, which can lead to the a change in the medication used. Due to this, it is important to understand what differs in patient’s blood plasma protein that can help identify good and bad responders to treatment. Through the analysis of differential expressed protein in good responders, it is possible to investigate which biochemical processes vary between them and therefore predict possible responses to better adapt patient’s treatment.

Identification of Human Blood Plasma Proteins Using Spike-In Peptides in Shotgun Proteomics

LC-MS/MS allows identification of thousands of proteins in the complex proteomes. However, a significant part of a proteome remains inaccessible for identification due to the absence or poor quality of MS/MS spectra. The method described herein allows identifying the desired proteins of human blood plasma by comparing aligned chromatographic data of digested by trypsin sample and the same sample with spikedin synthetic peptides. Identification of human blood plasma proteins is archived by assigning tandem mass spectra of spiked-in peptides to the corresponding aligned chromatographic peaks of proteolytic peptides. Using the described approach we have identified 19 low abundant proteins in human blood plasma, which corresponded to 19 synthetic peptides used in the study. SRM verification of the identifications with isotopically labelled standards (SIS) confirmed the presence in the plasma of above 17 proteins.

200+ Protein Concentrations in Healthy Human Blood Plasma: Targeted Quantitative SRM SIS Screening of Chromosomes 18, 13, Y, and the Mitochondrial Chromosome Encoded Proteome

This work continues the series of the quantitative measurements of the proteins encoded by different chromosomes in the blood plasma of a healthy person. Selected Reaction Monitoring with Stable Isotope-labeled peptide Standards (SRM SIS) and a gene-centric approach, which is the basis for the implementation of the international Chromosome-centric Human Proteome Project (C-HPP), were applied for the quantitative measurement of proteins in human blood plasma. Analyses were carried out in the frame of C-HPP for each protein-coding gene of the four human chromosomes: 18, 13, Y, and mitochondrial. Concentrations of proteins encoded by 667 genes were measured in 54 blood plasma samples of the volunteers, whose health conditions were consistent with requirements for astronauts. The gene list included 276, 329, 47, and 15 genes of chromosomes 18, 13, Y, and the mitochondrial chromosome, respectively. This paper does not make claims about the detection of missing proteins. Only 205 proteins (30.7%) were detected in the samples. Of them, 84, 106, 10, and 5 belonged to chromosomes 18, 13, and Y and the mitochondrial chromosome, respectively. Each detected protein was found in at least one of the samples analyzed. The SRM SIS raw data are available in the ProteomeXchange repository (PXD004374, PASS01192).

Modeling of a single nanoparticle interaction with the human blood plasma proteins.

When nanoparticles are introduced into a physiological environment, proteins and lipids immediately cover their surface, forming a protein "corona". It is well recognized that the corona structure influences the biological response of the body. Two deterministic models for corona formation of the human blood serum proteins around a single nanoparticle are presented and studied numerically in this paper. One of them is based on a coupled system of PDEs and involves diffusion of proteins toward the nanoparticle surface. The other one is described by ODEs and is a limit version of the first model as the protein diffusivity tends to infinity. The protein diffusivity influence on the temporal corona structure is studied in detail. Results are presented using figures and discussion.

Interaction of spin-labeled HPMA-based nanoparticles with human blood plasma proteins - the introduction of protein-corona-free polymer nanomedicine.

In this paper, we revised the current understanding of the protein corona that is created on the surface of nanoparticles in blood plasma after an intravenous injection. We have focused on nanoparticles that have a proven therapeutic outcome. These nanoparticles are based on two types of biocompatible amphiphilic copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA): a block copolymer, poly(ε-caprolactone) (PCL)-b-poly(HPMA), and a statistical HPMA copolymer bearing cholesterol moieties, which have been tested both in vitro and in vivo. We studied the interaction of nanoparticles with blood plasma and selected blood plasma proteins by electron paramagnetic resonance (EPR), isothermal titration calorimetry, dynamic light scattering, and cryo-transmission electron microscopy. The copolymers were labeled with TEMPO radicals at the end of hydrophobic PCL or along the hydrophilic HPMA chains to monitor changes in polymer chain dynamics caused by protein adsorption. By EPR and other methods, we were able to probe specific interactions between nanoparticles and blood proteins, specifically low- and high-density lipoproteins, immunoglobulin G, human serum albumin (HSA), and human plasma. It was found that individual proteins and plasma have very low binding affinity to nanoparticles. We observed no hard corona around HPMA-based nanoparticles; with the exception of HSA the proteins showed no detectable binding to the nanoparticles. Our study confirms that a classical "hard corona-soft corona" paradigm is not valid for all types of nanoparticles and each system has a unique protein corona that is determined by the nature of the NP material.

Biosystems Study of the Molecular Networks Underlying Hippocampal Aging Progression and Anti-aging Treatment in Mice.

Aging progression is a process that an individual encounters as they become older, and usually results from a series of normal physiological changes over time. The hippocampus, which contributes to the loss of spatial and episodic memory and learning in older people, is closely related to the detrimental effects of aging at the morphological and molecular levels. However, age-related genetic changes in hippocampal molecular mechanisms are not yet well-established. To provide additional insight into the aging process, differentially-expressed genes of 3- versus 24- and 29-month old mice were re-analyzed. The results revealed that a large number of immune and inflammatory response-related genes were up-regulated in the aged hippocampus, and membrane receptor-associated genes were down-regulated. The down-regulation of transmembrane receptors may indicate the weaker perception of environmental exposure in older people, since many transmembrane proteins participate in signal transduction. In addition, molecular interaction analysis of the up-regulated immune genes indicated that the hub gene, Ywhae, may play essential roles in immune and inflammatory responses during aging progression, as well as during hippocampal development. Our biological experiments confirmed the conserved roles of Ywhae and its partners between human and mouse. Furthermore, comparison of microarray data between advanced-age mice treated with human umbilical cord blood plasma protein and the phosphate-buffered saline control showed that the genes that contribute to the revitalization of advanced-age mice are different from the genes induced by aging. These results implied that the revitalization of advanced-age mice is not a simple reverse process of normal aging progression. Our data assigned novel roles of genes during aging progression and provided further theoretic evidence for future studies exploring the underlying mechanisms of aging and anti-aging-related disease therapy.

Red-emitting benzo[e]indolium probes for HSA based on the TICT characteristics

Human serum albumin (HSA) is the most abundant protein in human blood plasma. It plays an important role in many physiological functions, and the increase or decrease of HSA can exhibit the conditions of human health. Therefore, the accurate detection of HSA with high selectivity and sensitivity has a great clinical importance. We herein developed four red-emitting benzo[e]indolium fluorescent dyes, L1-L4, for probing HSA in a physiological buffer or human urine. Satisfactorily, L2 and L4 showed high selectivity and excellent sensitivity for HSA in both PBS buffer and human urine. L2 was completely embedded in the α-helices from subdomain IIA (Sudlow site I) of HSA, and the limit of detection (LOD) was 13.43mgL−1 in PBS and 8.91mgL−1 in urine, respectively. However, L4 inserted into the α-helices from subdomain IIA and IIIA (Sudlow site II) of HSA, and exhibited a lower LOD (1.75mgL−1 in PBS, 1.50mgL−1 in urine). Furthermore, the high tolerance of environmental pH and anti-interference of L2 and L4 enabled us to develop the promising molecular probes for HSA.

Structural aspects of graphitic carbon modified SBA-15 mesoporous silica and biological interactions with red blood cells and plasma proteins

Functional mesoporous materials have been worldwide studied for different applications. Mesoporous silicas are highlighted due to the synthetic possibilities for the preparation of such materials with different particle sizes and morphologies, and controlled pores sizes and structures. Moreover, the silica superficial silanol groups are explored in several chemical modifications, leading to functional materials with tuned functionalities and properties.In this work, an organo-functionalization and pyrolysis synthetic procedure is used to obtain graphitic carbon modified mesoporous SBA-15 silica. The carbon content was tuned during the functionalization step, and the graphitic nanodomains were formed in the pores surface and particles outer surface. Textural and small angle X-ray diffraction analysis accessed the presence of the carbon nanostructures inside the SBA-15 mesopores. Advanced microanalysis using electron energy loss spectroscopy coupled to a transmission electron microscope had confirmed the carbon distribution along the silica pores, which gives higher hydrophobicity and changed the interaction of the mesoporous material with biological systems.Finally, the influence of the surface modification with graphitic carbon species over the interaction with human red blood cells (hemolysis) and human blood plasma (protein corona formation) was elucidated for the very first time for this kind of functional materials. It was observed that the graphitic carbon species considerably reduced the hemolytic effect of the silica particles, and was responsible for modulating the loading and composition of the hard corona plasma proteins. This work deepness the fundamental knowledge on the interaction between such nanomaterials and biological systems, one step further the use of these modified silicas in biomedical applications.

Protection of proteins and lipids of blood plasma by different lithium salts under ethanol-induced oxidative damage

IntroductionThe creation of new lithium compounds with antioxidant activity is relevant problem for psychiatry. The aim of this work was study of the protective effect of lithium salts against ethanol-induced oxidative damage to proteins and lipids of human blood plasma in vitro.MethodsWe used lithium ascorbate and lithium carbonate 0.6 mmol/L which correspond to the therapeutic dose (in terms of lithium ions). Antioxidant carnosine (β-Ala-L-His) was used as comparison drug. We used the blood of 12 healthy donors. The heparinized blood samples were incubated in presence of tested preparations for one hour at 37 °C. The final ethanol concentration in samples was 0.5%. Oxidative modification of proteins was determined as the level of carbonylated proteins with 2.4–dinitrophenilhydrazine, lipid peroxidation products–as the level of TBA-reactive products by spectrometry. Statistical analysis was performed with “Statistika 10” program.ResultsThe addition of ethanol in the blood led to a significant increase in carbonylated proteins and TBA-reactive products in the plasma (carbonylated proteins: without ethanol 0.26 ± 0.01 nmol/mg of protein; with ethanol 0.33 ± 0.02 nmol/mg; TBA-reactive products: without–3.2 ± 0.1 nmol/mL; with–4.0 ± 0.2 nmol/mL, P &lt; 0.05). In the presence of carnosine such increase of oxidized products of biomolecules is not observed, i.e. carnosine had a protective effect against ethanol-induced oxidative damage. Lithium ascorbate showed a protective effect like carnosine. Lithium carbonate revealed no detectable influence on biomolecules in the conditions of our experiment.ConclusionLithium ascorbate has a protective effect on blood plasma proteins and lipids under ethanol-induced oxidative damage of biomolecules.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Targeted Proteomics and Absolute Protein Quantification for the Construction of a Stoichiometric Host-Pathogen Surface Density Model

Sepsis is a systemic immune response responsible for considerable morbidity and mortality. Molecular modeling of host-pathogen interactions in the disease state represents a promising strategy to define molecular events of importance for the transition from superficial to invasive infectious diseases. Here we used the Gram-positive bacterium Streptococcus pyogenes as a model system to establish a mass spectrometry based workflow for the construction of a stoichiometric surface density model between the S. pyogenes surface, the surface virulence factor M-protein, and adhered human blood plasma proteins. The workflow relies on stable isotope labeled reference peptides and selected reaction monitoring mass spectrometry analysis of a wild-type strain and an M-protein deficient mutant strain, to generate absolutely quantified protein stoichiometry ratios between S. pyogenes and interacting plasma proteins. The stoichiometry ratios in combination with a novel targeted mass spectrometry method to measure cell numbers enabled the construction of a stoichiometric surface density model using protein structures available from the protein data bank. The model outlines the topology and density of the host-pathogen protein interaction network on the S. pyogenes bacterial surface, revealing a dense and highly organized protein interaction network. Removal of the M-protein from S. pyogenes introduces a drastic change in the network topology, validated by electron microscopy. We propose that the stoichiometric surface density model of S. pyogenes in human blood plasma represents a scalable framework that can continuously be refined with the emergence of new results. Future integration of new results will improve the understanding of protein-protein interactions and their importance for bacterial virulence. Furthermore, we anticipate that the general properties of the developed workflow will facilitate the production of stoichiometric surface density models for other types of host-pathogen interactions.

Lithium ascorbate as a protector of human blood biomolecules under ethanol impact

Background: Alcoholism is an acute social problem worldwide for negative impact on health. This problem is closely associated with social stress and drinking traditions. Previously, it was established exhaustion of blood antioxidant in alcoholism patients. It requires development and investigation of substances with protective properties under ethanol impact, on both cells and biomolecules. Aims and Objectives: Lithium salts are widely used in medicine as mood stabilizers for mental pathologies, including alcoholism. In this work, we investigate lithium ascorbate for the protection of human blood plasma lipids and proteins under ethanol impact. Materials and Methods: Well-known antioxidants - carnosine and ascorbic acid - were used as reference drugs. Heparinized venous blood was used as an experimental substrate. The ethanol and tested substances in the form of water (physiological)solutions were added to blood in vitro. Protection effects were measured and estimated as concentrations of carbonyls proteins and products of lipid peroxidation in blood plasma. Results: It was shown similar protective action of lithium ascorbate and carnosine on human plasma biomolecules against damaging action of ethanol. No protective effect revealed for ascorbic acid. Conclusion: Lithium ascorbate and carnosine were proved to possess the protection effects for blood lipids and proteins under ethanol impact. Normothymic and bloodprotective properties are desirable for psychotropic drugs, and thus, lithium salts could be considered as prospective agents in the treatment of addictions and other pathologies associated with oxidative stress.