Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Archives of Toxicology, Год журнала: 2023, Номер 97(10), С. 2499 - 2574

Опубликована: Авг. 19, 2023

Abstract 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” characterized by low to mild levels oxidants involved in the regulation various biochemical transformations such carboxylation, hydroxylation, peroxidation, modulation signal transduction pathways Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related 2 (Nrf2) other processes. Increased ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result a harmful condition stress (“bad stress”). Although it widely accepted, that many chronic diseases are multifactorial origin, they share common denominator. Here we review importance mechanisms through which contributes pathological states an organism. Attention focused on chemistry ROS RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl nitric oxide, peroxynitrite), their role damage DNA, proteins, membrane lipids. Quantitative qualitative assessment biomarkers also discussed. Oxidative pathology cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s Parkinson’s Down syndrome), psychiatric (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, cancer), aging. The concerted action antioxidants ameliorate effect achieved antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), small molecular weight (vitamins C E, flavonoids, carotenoids, melatonin, ergothioneine, others). Perhaps one most effective vitamin first line defense against peroxidation promising approach appears be use flavonoids), showing weak prooxidant properties may boost cellular systems thus act preventive anticancer agents. Redox metal-based enzyme mimetic compounds potential pharmaceutical interventions sirtuins therapeutic targets for age-related anti-aging strategies

Язык: Английский

---

Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 24, 2025

Abstract Schizophrenia spectrum disorders (SSD) involve disturbances in the integration of perception, emotion and cognition. The corticolimbic system is an interacting set cortical subcortical brain regions critically involved this process. Understanding how neural circuitry molecular mechanisms within may contribute to development not only positive symptoms but also negative cognitive deficits SSD has been a recent focus intense research, as latter are adequately treated by current antipsychotic medications more strongly associated with poorer functioning long-term outcomes. This review synthesises developments examining dysfunction pathophysiology SSD, on neuroimaging advances related novel methodologies that enable data across different scales. We then integrate these findings inform identification therapeutic preventive targets for symptomatology. A range pharmacological interventions have shown initial promise correcting improving negative, treatment-resistant symptoms. discuss challenges opportunities still limited translation research into clinical practice. argue our knowledge role can be improved combining multiple modalities examine hypotheses spatial temporal scales, experimental utilising large-scale consortia advance biomarker identification. Translation practice will aided consideration optimal intervention timings, biomarker-led patient stratification, selective medications.

Язык: Английский

---

Understanding chronic inflammation: couplings between cytokines, ROS, NO, Cai2+, HIF-1α, Nrf2 and autophagy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

Chronic inflammation is an important component of many diseases, including autoimmune intracellular infections, dysbiosis and degenerative diseases. An element this state the mainly positive feedback between inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO), increased calcium, hypoxia-inducible factor 1-alpha (HIF-1α) stabilisation mitochondrial oxidative stress, which, under normal conditions, enhance response against pathogens. Autophagy nuclear erythroid 2-related 2 (Nrf2)-mediated antioxidant are negatively coupled with above-mentioned elements to maintain defence at a level appropriate severity infection. The current review first attempt build multidimensional model cellular self-regulation chronic inflammation. It describes feedbacks involved in explains possible pathways by which becomes chronic. multiplicity suggests that symptomatic treatment should focus on inhibiting multiple effectively suppress all dysregulated inflammation, calcium mito-stress other metabolic disturbances.

Язык: Английский

---

Glial cell deficits are a key feature of schizophrenia: implications for neuronal circuit maintenance and histological differentiation from classical neurodegeneration

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Abstract Dysfunctional glial cells play a pre-eminent role in schizophrenia pathophysiology. Post-mortem studies have provided evidence for significantly decreased cell numbers different brain regions of individuals with schizophrenia. Reduced are most pronounced oligodendroglia, but reduced astrocyte densities also been reported. This review highlights that oligo- and astroglial deficits key histopathological feature schizophrenia, distinct from typical changes seen neurodegenerative disorders. Significant oligodendrocytes may arise two ways: (i) demise mature functionally compromised oligodendrocytes; (ii) lack due to failed maturation progenitor cells. We analyse detail the controversy regarding astrocytes. Regardless their origin, several pathophysiological consequences. Among these, myelination number be important factor, resulting disconnectivity between neurons observed When die, it appears through degeneration, process which is basically reversible. Thus, therapeutic interventions help rescue or improve might viable option. Since antipsychotic treatment alone does not seem prevent loss deficits, there intense search new options. Current proposals range application antidepressants other chemical agents as well physical exercise engrafting healthy into brains patients.

Язык: Английский

---

Altered serum glutathione disulfide levels in acute relapsed schizophrenia are associated with clinical symptoms and response to electroconvulsive therapy

BMC Psychiatry, Год журнала: 2025, Номер 25(1)

Опубликована: Март 14, 2025

The pathophysiological mechanisms of schizophrenia are complex and not fully elucidated. This study aimed to investigate changes total glutathione (T-GSH), disulfide (GSSG), reduced (GSH), the GSH/GSSG ratio before after electroconvulsive therapy (ECT) for patients with acute relapse associations clinical symptoms. cohort included 110 55 healthy controls. All received 8–10 sessions ECT. Clinical symptoms were assessed using Positive Negative Syndrome Scale (PANSS). As compared controls, had decreased baseline GSSG levels (t = -2.115, p 0.036) elevated ratios 2.141, 0.034). Baseline negatively correlated both PANSS scores (beta -0.369, t -4.108, < 0.001) positive symptom -0.332, -3.730, 0.001), while positively improvements in (r 0.392, 0.293, 0.005) ECT treatment. In treatment responders, significantly increased -2.817, 0.006) 4.474, as ECT, T-GSH (B 0.734, OR 2.083, 95%CI:1.287–3.372, 0.003), -2.720, 0.066, 95%CI:0.011–0.390, -1.013, 0.363, 95%CI:0.142–0.930, 0.035) predictive improvement. Patients exhibit significant redox imbalance, may serve a potential biomarker evaluate predict outcomes.

Язык: Английский

---

Comparative study: trimetazidine versus olanzapine on cognitive dysfunction and behavioral changes in ketamine-induced psychosis model in mice

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Год журнала: 2025, Номер 61(1)

Опубликована: Апрель 29, 2025

Abstract Background Mitochondrial dysfunction and oxidative stress may contribute to schizophrenia. Negative symptoms cognitive in individuals with schizophrenia are resistant anti-psychotic medications, but physical exercise is an effective treatment. Exercise’s beneficial effects involve releasing irisin from skeletal muscle by activating mitochondrial peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC1-α). “Irisin enhances function boosting brain-derived neurotrophic factor (BDNF) through its antioxidant properties.” Schizophrenia patients struggle engage activity due their mitochondria. Trimetazidine improves increases release, offering alternative for schizophrenics dysfunction. The study compared trimetazidine olanzapine treating behavioral changes mice ketamine-induced psychosis. Researchers investigated the of on power, function, plasma level, correlation hippocampal BDNF MDA. Results Ketamine use led dysfunction, reduced BDNF, elevated MDA, decreased grip, irisin. improved MDA levels, function. Conclusions works like exercise, leading increase PGC1α Olanzapine induced less improvement a reduction grip.

Язык: Английский

---

Phenols and GABAA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Янв. 18, 2024

γ-Aminobutyric acid type A receptors (GABA Rs) are members of the pentameric ligand-gated ion channel (pLGIC) family, which widespread throughout invertebrate and vertebrate central nervous system. GABA Rs engaged in short-term changes neuronal concentrations chloride (Cl − ) bicarbonate (HCO 3 ions by their passive permeability through pore. regulated various structurally diverse phenolic substances ranging from simple phenols to complex polyphenols. The wide chemical structural variability suggest similar different binding sites on Rs, allowing them manifest themselves as activators, inhibitors, or allosteric ligands R function. Interest is associated with great potential for modulation, but also subsequent negative positive role neurological psychiatric disorders. This review focuses GABAergic deficit hypotheses during disorders induced phenols. We summarize structure–activity relationship general phenol groups concerning differential roles manifestation neuropsychiatric symptoms. describe analyze subunits manifesting neuropathologies molecular mechanisms underlying modulation Finally, we discuss how drugs can modulate activity via desensitization resensitization. demonstrate a novel pharmacological approach treat regulation receptor phosphorylation/dephosphorylation.

Язык: Английский

---

Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway’s Role on Schizophrenia’s Cognitive Impairments: A Multimodal Study in Patients and Mouse Models

Schizophrenia Bulletin, Год журнала: 2024, Номер 50(4), С. 913 - 923

Опубликована: Май 30, 2024

Abstract Background and Hypothesis This study investigated the role of medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. Study Design utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, optogenetics to investigate mPFC-BLA SCZ patients. In mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant deficits, which were addressed through stereotaxic injections an adeno-associated viral vector unveil neural connection between mPFC BLA. Results Significant disparities brain volume activity, particularly dorsolateral (DLPFC) BLA regions, found patients healthy controls. Additionally, we observed correlations indicating that reduced volumes DLPFC associated with lower function scores. Activation notably improved performance model mice, targeting excitatory or inhibitory neurons alone failing replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences mice. Notably, genes differentially expressed these also blood exosomes Conclusions Our research provides a comprehensive understanding PFC-BLA SCZ, underscoring its significance impairment offering novel diagnostic therapeutic avenues. our highlights potential exosomal mRNAs as noninvasive biomarkers for diagnosis, feasibility utility method.

Язык: Английский

---

The Preventive Effect of Zinc Sulfate against Olanzapine-Induced Testicular Toxicity in Male Rats

Biological Trace Element Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 10, 2024

Abstract Male infertility is a complex and multifactorial clinical condition affecting large population attributed to several factors, including perturbation in oxidative stress the level of essential trace elements. Oxidative exerts multiple issues related reproductive health, male infertility, decreased sperm motility, DNA damage, an increased susceptibility genetic disorders. Besides chemical toxins food allergens junk items, many drugs can also lead infertility. Olanzapine (OLZ), general antipsychotic drug, has been reported induce fertility. A great deal literature entails that supplementation zinc alleviate stress–related complications, This study investigates potential protective effects sulfate (ZnSO4) on OLZ-induced In present study, there were four treatment groups ( n = 6): group 1 as control (without any treatment); 2 treated with OLZ (10 mg/kg) orally daily for 6 weeks; 3 4 50 mg/kg 100 ZnSO4 respectively pre-exposed weeks. After completion treatment, biochemical analysis serum tissue samples demonstrated had compromised levels antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)) well elevated (oxidized (GSSG), malondialdehyde (MDA), nitric oxide (NO)) compared by significant extent p ≤ 0.05). However, significantly corrected all these dose-dependent way Other health indicators, like taurine, enzyme Q10, phosphatidylcholine, ascorbic acid, vitamin E, observed improve prominently ZnSO4. Intriguingly, fertility (sperm count testosterone) found be enhanced abnormalities both combination groups. The histological evaluation testis section agreed this investigation. Therefore, strongly advocates Zn ameliorate extent. Graphical Putative mechanism was involved preventive effect against vivo. generates free radicals stress-mediated toxicity target organs testes evidenced alteration markers histology. ions from act agent blunting most OLZ-perturbed redox histology consequently improving parameters.

Язык: Английский

---

IUPHAR Themed Review: The Gut Microbiome in Schizophrenia

Pharmacological Research, Год журнала: 2024, Номер unknown, С. 107561 - 107561

Опубликована: Дек. 1, 2024

Gut microbial dysbiosis or altered gut consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on architecture disruption of bacterial phyla ratios, diminished taxonomic diversity, attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, rationalised co-pharmacotherapy, show promise attenuating antipsychotic-induced metabolic disruptions while enhancing efficacy. Harnessing such insights, precision medicine approaches transform antipsychotic prescribing practices by identifying patients at risk side based their profiles. This IUPHAR review collates current literature landscape axis its intricate relationship advocating for integrating microbiome assessments management. Such fundamental shift proposing microbiome-informed prescriptions optimise efficacy reduce adverse impacts would align treatments safety, prioritising 'gut-neutral' gut-favourable drugs safeguard long-term patient outcomes therapy.

Язык: Английский

---