Infections have been a major cause of disease throughout the history of humans on earth. With the introduction of antibiotics, it was thought that infections had been conquered. However, bacteria ...have been able to develop resistance to antibiotics at an exponentially increasing rate. The growing threat from multi-drug resistant organisms calls for intensive action to prevent the emergence of totally resistant and untreatable infections. Novel, non-invasive, non-antibiotic strategies are needed that act more efficiently and faster than current antibiotics. One promising alternative is antimicrobial photodynamic inactivation (APDI), an approach that produces reactive oxygen species when dyes and light are combined. So far, it has been questionable if bacteria can develop resistance against APDI. This review paper gives an overview of recent studies concerning the susceptibility of bacteria towards oxidative stress, and suggests possible mechanisms of the development of APDI-resistance that should at least be addressed. Some ways to potentiate APDI and also to overcome future resistance are suggested.
Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and ...insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.
Oxidative stress plays a major role in the life and death of mammalian spermatozoa. These gametes are professional generators of reactive oxygen species (ROS), which appear to derive from three ...potential sources: sperm mitochondria, cytosolic L-amino acid oxidases, and plasma membrane Nicotinamide adenine dinucleotide phosphate oxidases. The oxidative stress created via these sources appears to play a significant role in driving the physiological changes associated with sperm capacitation through the stimulation of a cyclic adenosine monophosphate/Protein kinase A phosphorylation cascade, including the activation of Extracellular signal regulated kinase-like proteins, massive up-regulation of tyrosine phosphorylation in the sperm tail, as well as the induction of sterol oxidation. When generated in excess, however, ROS can induce lipid peroxidation that, in turn, disrupts membrane characteristics that are critical for the maintenance of sperm function, including the capacity to fertilize an egg. Furthermore, the lipid aldehydes generated as a consequence of lipid peroxidation bind to proteins in the mitochondrial electron transport chain, triggering yet more ROS generation in a self-perpetuating cycle. The high levels of oxidative stress created as a result of this process ultimately damage the DNA in the sperm nucleus; indeed, DNA damage in the male germ line appears to be predominantly induced oxidatively, reflecting the vulnerability of these cells to such stress. Extensive evaluation of antioxidants that protect the spermatozoa against oxidative stress while permitting the normal reduction-oxidation regulation of sperm capacitation is therefore currently being undertaken, and has already proven efficacious in animal models.
Nephrotoxicity is the hallmark of anti-neoplastic drug metabolism that causes oxidative stress. External chemical agents and prescription drugs release copious amounts of free radicals originating ...from molecular oxidation and unless sustainably scavenged, they stimulate membrane lipid peroxidation and disruption of the host antioxidant mechanisms. This review aims to provide a comprehensive collection of potential cytoprotective remedies in surmounting the most difficult aspect of cancer therapy as well as preventing renal oxidative stress by other means.
Over 400 published research and review articles spanning several decades were scrutinised to obtain the relevant data which is presented in 3 categories; sources, mechanisms, and mitigation of renal oxidative stress.
Drug and chemical-induced nephrotoxicity commonly manifests as chronic or acute kidney disease, nephritis, nephrotic syndrome, and nephrosis. Renal replacement therapy requirements and mortalities from end-stage renal disease are set to rapidly increase in the next decade for which 43 different cytoprotective compounds which have the capability to suppress experimental nephrotoxicity are described.
The renal system performs essential homeostatic functions that play a significant role in eliminating toxicants, and its accumulation and recurrence in nephric tissues results in tubular degeneration and subsequent renal impairment. Global statistics of the latest chronic kidney disease prevalence is 13.4 % while the end-stage kidney disease requiring renal replacement therapy is 4–7 million per annum. The remedial compounds discussed herein had proven efficacy against nephrotoxicity manifested consequent to impaired antioxidant mechanisms in preclinical models produced by renal oxidative stress activators.
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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 to upregulation of cellular antioxidant capacity to maintain ROS levels below a toxic threshold. Combining drugs that induce high levels of ROS with compounds that suppress cellular antioxidant capacity by depleting antioxidant systems glutathione (GSH), superoxide dismutase (SOD), and thioredoxin (TRX) and/or targeting glucose metabolism represents a potential anticancer strategy. In AD, free metals and/or Aβ:metal complexes may cause damage to biomolecules in the brain (via Fenton reaction), including DNA. Metal chelation, based on the application of selective metal chelators or metal delivery, may induce neuroprotective signaling and represents a promising therapeutic strategy. This review examines therapeutic strategies based on the modulation of oxidative stress in cancer and AD.
BackgroundPersistence of myofibroblasts is believed to contribute to the development of fibrosis in idiopathic pulmonary fibrosis (IPF). Transforming growth factor β1 (TGFβ1) irreversibly converts ...fibroblasts into pathological myofibroblasts, which express smooth muscle α-actin (α-SMA) and produce extracellular matrix proteins, such as procollagen I (α1). Reactive oxygen species produced by NADPH oxidases (NOXs) have been shown to regulate cell differentiation. It was hypothesised that NOX could be expressed in parenchymal pulmonary fibroblasts and could mediate TGFβ1-stimulated conversion of fibroblasts into myofibroblasts.MethodsFibroblasts were cultured from the lung of nine controls and eight patients with IPF. NOX4, α-SMA and procollagen I (α1) mRNA and protein expression, reactive oxygen species production and Smad2/3 phosphorylation were quantified, in the absence and in the presence of incubation with TGFβ1. Migration of platelet-derived growth factor (PDGF)-induced fibroblasts was also assessed.ResultsIt was found that (1) NOX4 mRNA and protein expression was upregulated in pulmonary fibroblasts from patients with IPF and correlated with mRNA expression of α-SMA and procollagen I (α1) mRNA; (2) TGFβ1 upregulated NOX4, α-SMA and procollagen I (α1) expression in control and IPF fibroblasts; (3) the change in α-SMA and procollagen I (α1) expression in response to TGFβ1 was inhibited by antioxidants and by a NOX4 small interfering RNA (siRNA); (4) NOX4 modulated α-SMA and procollagen I (α1) expression by controlling activation of Smad2/3; and (5) NOX4 modulated PDGF-induced fibroblast migration.ConclusionNOX4 is critical for modulation of the pulmonary myofibroblast phenotype in IPF, probably by modulating the response to TGFβ1 and PDGF.
NF-κB in oxidative stress Lingappan, Krithika
Current opinion in toxicology,
02/2018, Letnik:
7
Journal Article
Recenzirano
Odprti dostop
The transcription factor nuclear factor-κB (NF-κB) modulates gene expression in diverse cellular processes such as innate immune response, embryogenesis and organ development, cell proliferation and ...apoptosis, and stress responses to a variety of noxious stimuli. When cellular production of reactive oxygen species (ROS) overwhelms its antioxidant capacity, it leads to a state of oxidative stress, which in turn contributes to the pathogenesis of several human diseases. Different models of oxidative stress have been studied to elucidate the effects of oxidant stress on NF-κB related activities. ROS can both activate and repress NF-κB signaling in a phase and context dependent manner. The NF-κB pathway can have both anti- and pro-oxidant roles in the setting of oxidative stress. In this review, we focus on role of oxidative stress on different mediators of the NF-κB pathway, and the role of NF-κB activation in the modulation of oxidative stress. A greater understanding of the complex interplay between the NF-κB signaling and oxidative stress may lead to the development of therapeutic strategies for the treatment of a myriad of human diseases for which oxidative stress has an etiologic role.
•Modulation of the NF-κB pathway by oxidative stress is cell type and context specific.•Reactive oxygen species have bidirectional effects on NF-KB signaling depending on the duration and context of exposure.•Activation of NF-κB pathway can have both anti- and pro-oxidant effects.
This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different ...structures and sources, and following different mechanisms of action) in fighting against oxidative stress.
Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite.
Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage.
The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases.
The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers.
The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.
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•Oxidative stress initiates structure and function alterations of key biomolecules.•The oxidant/antioxidant unbalance activates factors responsible for cell injury.•Reactive oxygenated/nitrogenated species become the source of disease occurrence.•General and specific antioxidant mechanisms prevent the oxidative damage.•Prooxidative effects may occur in some cases, like in the presence of transition metal ions.
"Oxidative stress" as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this term. This concept has its merits and ...its pitfalls. Among the merits is the notion, elicited by the combined two terms of (i) aerobic metabolism as a steady-state redox balance and (ii) the associated potential strains in the balance as denoted by the term, stress, evoking biological stress responses. Current research on molecular redox switches governing oxidative stress responses is in full bloom. The fundamental importance of linking redox shifts to phosphorylation/dephosphorylation signaling is being more fully appreciated, thanks to major advances in methodology. Among the pitfalls is the fact that the underlying molecular details are to be worked out in each particular case, which is bvious for a global concept, but which is sometimes overlooked. This can lead to indiscriminate use of the term, oxidative stress, without clear relation to redox chemistry. The major role in antioxidant defense is fulfilled by antioxidant enzymes, not by small-molecule antioxidant compounds. The field of oxidative stress research embraces chemistry, biochemistry, cell biology, physiology and pathophysiology, all the way to medicine and health and disease research.
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