Search Results (54)

RNA–DNA differences (RDDs) challenge the traditional view of RNA as a faithful copy of DNA, arising through RNA editing, transcriptional errors, and oxidative damage. Reactive oxygen species (ROS) play a central role, inducing lesions like 8-oxo-guanine that compromise transcription and translation, leading to dysfunctional proteins. This review explores the biochemical basis of RDDs, their exacerbation under oxidative stress, and their dual roles in cellular adaptation and disease. RDDs contribute to genomic instability and are implicated in cancers, neurodegenerative disorders, and autoimmune diseases, while also driving phenotypic diversity. Drawing on terrestrial and spaceflight studies, we highlight the intersection of oxidative stress, RDD formation, and cellular dysfunction, proposing innovative mitigation approaches. Advancements in RDD detection and quantification, along with ROS management therapies, offer new avenues to restore cellular homeostasis and promote resilience. By positioning RDDs as a hallmark of genomic entropy, this review underscores the limits of biological adaptation. Furthermore, the prevalence of guanine-rich codons in antioxidant genes increases their susceptibility to ROS-induced oxidative lesions, linking redox stress, genomic instability, and constrained adaptation. These insights have profound implications for understanding aging, disease progression, and adaptive mechanisms in both terrestrial and space environments. Full article

Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature of aging, and telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging is also associated with mitochondrial dysfunction, leading to increased reactive oxygen species (ROS) that exacerbate cellular damage and promote apoptosis. Elevated ROS levels can damage telomeres by oxidizing guanine and disrupting their regulation. Conversely, telomere damage impacts mitochondrial function, and activation of telomerase has been shown to reverse this decline. A critical link between telomere shortening and mitochondrial dysfunction is the DNA damage response, which activates the tumor suppressor protein p53, resulting in reduced mitochondrial biogenesis and metabolic disruptions. This highlights the bidirectional relationship between telomere maintenance and mitochondrial function. This review explores the complex interactions between telomeres and mitochondria across various cell types, from fibroblasts to sperm cells, shedding light on the interconnected mechanisms underlying aging and cellular function. Full article

In this study, the antioxidant and prooxidant potency of protocatechuic aldehyde (PCA) was evaluated using density functional theory (DFT). The potency of direct scavenging of hydroperoxyl (HOO^•) and lipid peroxyl radicals (modeled by vinyl peroxyl, H₂C=CHOO^•) involved in lipid peroxidation was estimated. The repair of oxidative damage in biomolecules (lipids, proteins and nucleic acids) and the prooxidant ability of PCA phenoxyl radicals were considered. The repairing potency of PCA was investigated for damaged tryptophan, cysteine, leucine, DNA base guanine and linolenic acid. The thermodynamics and kinetics of the single electron transfer (SET) and formal hydrogen atom transfer (fHAT) mechanisms underlying the studied processes were investigated under physiological conditions in aqueous and lipid environments using the SMD/M06-2X/6-311++G(d,p) level of theory. Sequestration of catalytic Fe²⁺ and Fe³⁺ ions by PCA, which prevents HO^• production via Fenton-like reactions, was modeled. Molecular docking was used to study the inhibitory capability of PCA against xanthine oxidase (XO), one of the enzymes producing reactive oxygen species. The attained results show that PCA has the capability to scavenge lipid peroxyl radicals, repair damaged tryptophan, leucine and guanine, chelate catalytic iron ions and inhibit XO. Thus, PCA could be considered a possible multifunctional antioxidant. Full article

In this review, we focus on the one-electron oxidation of DNA, which is a multipart event controlled by several competing factors. We will discuss the oxidation free energies of the four nucleobases and the electron detachment from DNA, influenced by specific interactions like hydrogen bonding and stacking interactions with neighboring sites in the double strand. The formation of a radical cation (hole) which can migrate through DNA (hole transport), depending on the sequence-specific effects and the allocation of the final oxidative damage, is also addressed. Particular attention is given to the one-electron oxidation of ds-ODN containing G:C pairs, including the complex mechanism of the deprotonation vs. hydration steps of a G:C^•+ pair, as well as to the modes of formation of the two guanyl radical tautomers after deprotonation. Among the reactive oxygen species (ROS) generated in aerobic organisms by cellular metabolisms, several oxidants react with DNA. The mechanism of stable product formation and their use as biomarkers of guanine oxidation in DNA damage are also addressed. Full article

In this work, we conducted a study of the interaction between DNA and favipiravir (FAV). This chemotherapeutic compound is an antiviral drug for the treatment of COVID-19 and other infections caused by RNA viruses. This paper examines the electroanalytical characteristics of FAV. The determined concentrations correspond to therapeutically significant ones in the range of 50–500 µM (R² = 0.943). We have shown that FAV can be electro-oxidized around the potential of +0.96 V ÷ +0.98 V (vs. Ag/AgCl). A mechanism for electrochemical oxidation of FAV was proposed. The effect of the drug on DNA was recorded as changes in the intensity of electrochemical oxidation of heterocyclic nucleobases (guanine, adenine and thymine) using screen-printed graphite electrodes modified with single-walled carbon nanotubes and titanium oxide nanoparticles. In this work, the binding constants (Kb) of FAV/dsDNA complexes for guanine, adenine and thymine were calculated. The values of the DNA-mediated electrochemical decline coefficient were calculated as the ratio of the intensity of signals for the electrochemical oxidation of guanine, adenine and thymine in the presence of FAV to the intensity of signals for the electro-oxidation of these bases without drug (S, %). Based on the analysis of electrochemical parameters, values of binding constants and spectral data, intercalation was proposed as the principal mechanism of the antiviral drug FAV interaction with DNA. The interaction with calf thymus DNA also confirmed the intercalation mechanism. However, an additional mode of interaction, such as a damage effect together with electrostatic interactions, was revealed in a prolonged exposure of DNA to FAV. Full article

The guanine oxidized (GO) system of Bacillus subtilis, composed of the YtkD (MutT), MutM and MutY proteins, counteracts the cytotoxic and genotoxic effects of the oxidized nucleobase 8-OxoG. Here, we report that in growing B. subtilis cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H₂O₂) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of B. subtilis to evolve and survive the noxious effects of oxidative stress were dissected. Genetic and biochemical evidence indicated that the synthesis of KatA was exacerbated, in a PerR-independent manner, and the transcriptional coupling repair factor, Mfd, contributed to HPHR and HPM of the ΔGO strain. Moreover, these phenotypes are associated with wider pleiotropic effects, as revealed by a global proteome analysis. The inactivation of the GO system results in the upregulated production of KatA, and it reprograms the synthesis of the proteins involved in distinct types of cellular stress; this has a direct impact on (i) cysteine catabolism, (ii) the synthesis of iron–sulfur clusters, (iii) the reorganization of cell wall architecture, (iv) the activation of AhpC/AhpF-independent organic peroxide resistance, and (v) increased resistance to transcription-acting antibiotics. Therefore, to contend with the cytotoxic and genotoxic effects derived from the accumulation of 8-OxoG, B. subtilis activates the synthesis of proteins belonging to transcriptional regulons that respond to a wide, diverse range of cell stressors. Full article

Among the bases of DNA, guanine is the most easily oxidized. Imidazolone (Iz) is a guanine oxidative damage, and we sought to generate Iz-containing oligomers. In this paper, we describe the methods and conditions to increase the yield of Iz by employing photooxidation reactions using light-emitting diodes (LEDs) with emission wavelengths of 365 nm and 450 nm. For photooxidation performed with the 450 nm LED source at light intensities of 2.75–275 mW/cm², peak yields of Iz were 35% at light intensities of 27.5 and 68.8 mW/cm². For reactions performed with the 365 nm LED source at light intensities of 5.12–512 mW/cm², the peak yield of Iz was 34% at a light intensity of 51.2 mW/cm². By varying the irradiation time, the maximum yield of Iz (34–35%) was obtained with irradiation times of 5–20 min using the 450 nm LED source at an intensity of 13.8 mW/cm². Using the 365 nm LED source at an intensity of 25.6 mW/cm², the maximum Iz yield obtained was 31% at irradiation times of 2–5 min. Thus, we obtained conditions that can provide an Iz yield of up to 35%. Full article

Gastroesophageal reflux disease (GERD) leads to the accumulation of bile-induced reactive oxygen species and oxidative stress in esophageal tissues, causing inflammation and DNA damage. The progression sequence from healthy esophagus to GERD and eventually cancer is associated with a microbiome shift. Lactobacillus species are commensal organisms known for their probiotic and antioxidant characteristics in the healthy esophagus. This prompted us to investigate how Lactobacilli survive in a bile-rich environment during GERD, and to identify their interaction with the bile-injured esophageal cells. To model human reflux conditions, we exposed three Lactobacillus species (L. acidophilus, L. plantarum, and L. fermentum) to bile. All species were tolerant to bile possibly enabling them to colonize the esophageal epithelium under GERD conditions. Next, we assessed the antioxidant potential of Lactobacilli and role in bile injury repair: we measured bile-induced DNA damage using the ROS marker 8-oxo guanine and COMET assay. Lactobacillus addition after bile injury accelerated repair of bile-induced DNA damage through recruitment of pH2AX/RAD51 and reduced NFκB-associated inflammation in esophageal cells. This study demonstrated anti-genotoxic and anti-inflammatory effects of Lactobacilli, making them of significant interest in the prevention of Barrett’s esophagus and esophageal adenocarcinoma in patients with GERD. Full article

In this proof-of-concept study, gold nanoparticles (AuNPs) were immobilized on glassy carbon electrode (GCE) surfaces using a surface-anchored diazonium salt of 4-aminothiophenol (GCE-Ph-S-AuNPs). X-ray photoelectron spectroscopy (XPS) studies confirmed the attachment of the AuNPs via 4-thiophenol onto the surface of the modified electrode. Differential pulse voltammetry (DPV) was performed for the simultaneous determination of guanine (G) and 8-hydroxyguanine (8-OH-G). The calibration curves were linear up to 140 µM and 60 µM with a limit of detection of 0.02 µM and 0.021 µM for G and 8-OH-G, respectively. Moreover, chronoamperometric studies were carried out for the determination of diffusion coefficients of 8-OH-G and G. The GCE-Ph-S-AuNPs were also applied in genomic DNA-spiked samples for the determination of G and 8-OH-G with recovery rates between 98.5% and 103.3%. The novel electrochemical surface provided a potential platform for the sensitive detection of 8-OH-G related to oxidative stress-induced DNA damage in clinical studies. Full article

Energy transfer to ground state triplet molecular oxygen results in the generation of singlet molecular oxygen (¹O₂), which has potent oxidizing ability. Irradiation of light, notably ultraviolet A, to a photosensitizing molecule results in the generation of ¹O₂, which is thought to play a role in causing skin damage and aging. It should also be noted that ¹O₂ is a dominant tumoricidal component that is generated during the photodynamic therapy (PDT). While type II photodynamic action generates not only ¹O₂ but also other reactive species, endoperoxides release pure ¹O₂ upon mild exposure to heat and, hence, are considered to be beneficial compounds for research purposes. Concerning target molecules, ¹O₂ preferentially reacts with unsaturated fatty acids to produce lipid peroxidation. Enzymes that contain a reactive cysteine group at the catalytic center are vulnerable to ¹O₂ exposure. Guanine base in nucleic acids is also susceptible to oxidative modification, and cells carrying DNA with oxidized guanine units may experience mutations. Since ¹O₂ is produced in various physiological reactions in addition to photodynamic reactions, overcoming technical challenges related to its detection and methods used for its generation would allow its potential functions in biological systems to be better understood. Full article

The current study was focused on the potential of pure P25 TiO₂ nanoparticles (NPs) and Fe(1%)-N co-doped P25 TiO₂ NPs to induce cyto- and genotoxic effects in MRC-5 human pulmonary fibroblasts. The oxidative lesions of P25 NPs were reflected in the amount of 8-hydroxydeoxyguanosine accumulated in DNA and the lysosomal damage produced, but iron-doping partially suppressed these effects. However, neither P25 nor Fe(1%)-N co-doped P25 NPs had such a serious effect of inducing DNA fragmentation or activating apoptosis signaling. Moreover, oxo-guanine glycosylase 1/2, a key enzyme of the base excision repair mechanism, was overexpressed in response to the oxidative DNA deterioration induced by P25 and P25-Fe(1%)-N NPs. Full article

Telomeres are dynamic DNA nucleoprotein structures located at the end of chromosomes where they maintain genomic stability. Due to the end replication problem, telomeres shorten with each cell division. Critically short telomeres trigger cellular senescence, which contributes to various degenerative and age-related diseases, including chronic kidney diseases (CKDs). Additionally, other factors such as oxidative stress may also contribute to accelerated telomere shortening. Indeed, telomeres are highly susceptible to oxidative damage due to their high guanine content. Here, we provide a comprehensive review of studies examining telomere length (TL) in CKDs to highlight the association between TL and the development and progression of CKDs in humans. We then focus on studies investigating TL in patients receiving kidney replacement therapy. The mechanisms of the relationship between TL and CKD are not fully understood, but a shorter TL has been associated with decreased kidney function and the progression of nephropathy. Interestingly, telomere lengthening has been observed in some patients in longitudinal studies. Hemodialysis has been shown to accelerate telomere erosion, whereas the uremic milieu is not reversed even in kidney transplantation patients. Overall, this review aims to provide insights into the biological significance of telomere attrition in the pathophysiology of kidney disease, which may contribute to the development of new strategies for the management of patients with CKDs. Full article

The production of reactive oxygen species (ROS) in the brain is homeostatically controlled and contributes to normal neural functions. Inefficiency of control mechanisms in brain aging or pathological conditions leads to ROS overproduction with oxidative neural cell damage and degeneration. Among the compounds showing therapeutic potential against neuro-dysfunctions induced by oxidative stress are the guanine-based purines (GBPs), of which the most characterized are the nucleoside guanosine (GUO) and the nucleobase guanine (GUA), which act differently. Indeed, the administration of GUO to in vitro or in vivo models of acute brain injury (ischemia/hypoxia or trauma) or chronic neurological/neurodegenerative disorders, exerts neuroprotective and anti-inflammatory effects, decreasing the production of reactive radicals and improving mitochondrial function via multiple molecular signals. However, GUO administration to rodents also causes an amnesic effect. In contrast, the metabolite, GUA, could be effective in memory-related disorders by transiently increasing ROS production and stimulating the nitric oxide/soluble guanylate cyclase/cGMP/protein kinase G cascade, which has long been recognized as beneficial for cognitive function. Thus, it is worth pursuing further studies to ascertain the therapeutic role of GUO and GUA and to evaluate the pathological brain conditions in which these compounds could be more usefully used. Full article

This article is devoted to a novel class of antimicrobial agents: nanocomposites composed of spherical silica and silver ions located at the silica’s surface with the assumed distribution. Such materials are in high demand due to the increasing threat from bacterial strains that are becoming resistant to currently known antibiotics. In particular, we focus on materials that make it possible to limit the growth of bacterial colonies on a variety of tactile surfaces. In this paper, we present a method for preparing a silica-based nanocomposite containing silver ions and the analysis of their antimicrobial properties. Our research revealed that the presence of tested nanocomposite induces very high oxidative stress in the bacteria cell, damaging and modifying bacterial DNA, creating oxidized guanines, cytosines, or adenines, which causes its very rapid destruction, leading to cell death. Full article

Aicardi–Goutières syndrome (AGS) is a rare encephalopathy characterized by neurological and immunological features. Mitochondrial dysfunctions may lead to mitochondrial DNA (mtDNA) release and consequent immune system activation. We investigated the role of mitochondria and mtDNA in AGS pathogenesis by studying patients mutated in RNASEH2B and RNASEH2A genes. Lymphoblastoid cell lines (LCLs) from RNASEH2A- and RNASEH2B-mutated patients and healthy control were used. Transmission Electron Microscopy (TEM) and flow cytometry were used to assess morphological alterations, reactive oxygen species (ROS) production and mitochondrial membrane potential variations. Seahorse Analyzer was used to investigate metabolic alterations, and mtDNA oxidation and VDAC1 oligomerization were assessed by immunofluorescence. Western blot and RT-qPCR were used to quantify mtTFA protein and mtDNA release. Morphological alterations of mitochondria were observed in both mutated LCLs, and loss of physiological membrane potential was mainly identified in RNASEH2A LCLs. ROS production and 8-oxoGuanine levels were increased in RNASEH2B LCLs. Additionally, the VDAC1 signal was increased, suggesting a mitochondrial pore formation possibly determining mtDNA release. Indeed, higher cytoplasmic mtDNA levels were found in RNASEH2B LCLs. Metabolic alterations confirmed mitochondrial damage in both LCLs. Data highlighted mitochondrial alterations in AGS patients’ LCLs suggesting a pivotal role in AGS pathogenesis. Full article