Reactive oxygen species and oxidative stress in acute pancreatitis:Pathogenesis and new therapeutic interventions

Acute pancreatitis(AP)is a common acute gastrointestinal disorder affecting approximately 20%of patients with systemic inflammatory responses that may cause pancreatic and peripancreatic fat necrosis.This condition often progresses to multiple organ failure,significantly increasing morbidity and mortality.Oxidative stress,characterized by an imbalance between the body’s reactive oxygen species(ROS)and antioxidants,activates the inflammatory signaling pathways.Although the pathogenesis of AP is not fully understood,ROS are increasingly recognized as critical in the disease's progression and development.Modulating the oxidative stress pathway has shown efficacy in mitigating the progression of AP.Despite numerous basic studies examining this pathway,comprehensive reviews of recent research remain sparse.This systematic review offers an in-depth examination of the critical role of oxidative stress in the pathogenesis and progression of AP and evaluates the therapeutic potential of antioxidant interventions in its management.

Oxidation of ciprofloxacin by the synergistic effect of DBD plasma and persulfate:reactive species and influencing factors analysis

A synergistic system of water falling film dielectric barrier discharge(DBD)plasma and persulfate(PS)was set up and used for oxidizing ciprofloxacin(CIP)in water.Results of reactive species formation in the DBD-only system as well as the DBD–PS system verified the PS activation in the DBD system.Influencing factors on CIP degradation and the degradation process were also been studied.The obtained results showed that the presence of PS could greatly improve the degradation and mineralization of CIP and that the degradation efficiency could reach 97.73%after only 40 min treatment with 4 m M PS addition.The increase of PS concentration,the lower CIP concentration,the acidic solution p H and the addition of metal ions(Fe^(2+)and Cu^(2+))enhanced the CIP degradation,while the existence of Cl^(-)and HCO_(3)^(-)had a negative effect.The experiments related to scavenger addition confirmed the contribution of the main reactive species to the CIP oxidation.Three probable degradation pathways were proposed by analyzing the inorganic ions and organic byproducts formed during the CIP degradation.The toxicity evaluation results of the CIP and its intermediates confirmed the effectiveness of the DBD–PS synergistic system.

Effects of Nitric Oxide on the Germination of Wheat Seeds and Its Reactive Oxygen Species Metabolisms Under Osmotic Stress

Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).

Novel insights into the mechanism of reactive oxygen species-mediated neurodegeneration

Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,but rather it appears that a self-destructive process is in action.Oxidative stress is a well-known inducer of neurodegenerative pathways:neuronal cell death and neurite degeneration.Although oxidative stress exerts cytotoxic effects leading to neuronal loss,the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown.We previously reported that reactive oxygen species generated by NADPH oxidases induce activation of the E3 ubiquitin ligase ZNRF1 in neurons,which promotes neurite degeneration.In this process,the phosphorylation of an NADPH oxidase subunit p47-phox at the 345serine residue serves as an important checkpoint to initiate the ZNRF1-dependent neurite degeneration.Evidence provides new insights into the mechanism of reactive oxygen species-mediated neurodegeneration.In this review,we focus specifically on reactive oxygen species-induced neurite degeneration by highlighting a phosphorylation-dependent regulation of the molecular interaction between ZNRF1 and the NADPH oxidase complex.

Characterization of the Long-Term Interaction between Intracellular Reactive Oxygen Species and Oxidative DNA Damage in Murine Lin^-/Sca-1⁺Cells Exposed to Ionizing Radiation

Mutations in the Sfpi1 gene are essential for the development of radia-tion-induced acute myeloid leukemia. In this study, we investigated long-term interaction among immature hematopoietic cell number, intra-cellular reactive oxygen species contents, and oxidative DNA damage fre-quency after irradiation. Lin-/Sca-1+ cells were isolated from C3H/HeN mice on days 1 - 400 after 0 - 3 Gy total body irradiation. On days 1 - 7, the number of surviving cells decreased and reached a minimum;however, the number of cells gradually recovered until day 200. Intracellular reactive oxygen species contents significantly increased from day 1 to day 30. In addition, the frequency of oxidative DNA damage tended to increase from day 1 and day 30, and that at day 30 was significantly increased in the 3 Gy group compared with that in the control group. In contrast, decreased cell number, increased intracellular reactive oxygen species content, and decreased oxidative DNA damage frequency were observed on day 400. These results suggested that oxidative DNA damage was involved in intracellular reactive oxygen species generation induced by cell proliferation to compensate for cell death after irradiation.

Spotlights on immunological effects of reactive nitrogen species: When inflammation says nitric oxide

Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still represent the prototype of NO-producing cells. Notwithstanding, additional cell subsets belonging to both innate and adaptive immunity have been documented to sustain NO propagation by means of the enzymatic activity of different nitric oxide synthase isoforms. Furthermore, due to its chemical characteristics, NO could rapidly react with other free radicals to generate different reactive nitrogen species(RNS), which have been intriguingly associated with many pathological conditions. Nonetheless, the plethora of NO/RNS-mediated effects still remains extremely puzzling. The aim of this manuscript is to dig into the broad literature on the topic to provide intriguing insights on NO-mediated circuits within immune system. We analysed NO and RNS immunological clues arising from their biochemical properties, immunomodulatory activities and finally dealing with their impact on different pathological scenarios with far prompting intriguing perspectives for their pharmacological targeting.

Reactive oxygen species, nitric oxide and plant cell death associated with caspase-like protease activity during somatic embryogenesis in Fraxinus mandshurica

Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica were used as explants. Mitochondrial structure and function, caspase-3-like protease activity, hydrogen peroxide metabolism, and nitric oxide accumulation induced by high concentrations of sucrose and plant growth regulators were studied. The results show that plant growth regulators induced somatic embryogenesis and also promoted explant browning. High sucrose concentrations had similar effects. High concentrations of sucrose and plant growth regulators led to the accumulation of hydrogen peroxide and nitric oxide which induced changes in mitochondrial structure and function such as modifications in mitochondrial morphology, increased membrane permeability, decreased membrane potential, and the release of cytochrome c into the cytoplasm. An increase in caspase-3-like protease activity triggered programmed cell death in some browning explant cells. During somatic embryogenesis there were increased activities of superoxide dismutase, peroxidase, and catalase, which are associated with hydrogen peroxide metabolism and jointly maintain reactive oxygen species levels. Intracellular nitric oxide synthase and nitrate reductase activities were not significantly correlated with nitric oxide content. Instead, intracellular nitric oxide may be derived from non-enzymatic reactions. Our results indicate that hydrogen peroxide and nitric oxide may function as signals, playing key roles in somatic embryogenesis and programmed cell death of explant cells of F. mandshurica. The interaction between nitric oxide and reactive oxygen species determines the occurrence of programmed cell death in explant cells;somatic embryogenesis and programmed cell death are positively regulated by hydrogen peroxide. However, the regulation of nitric oxide is complex.

Production of reactive oxygen species and expression of inducible nitric oxide synthase in rat isolated Kupffer cells stimulated by Leptospira interrogans and Borrelia burgdorfen

AIM： To evaluate the production of reactive oxygen species （ROS） and the expression of inducible nitric oxide synthase （iNOS） in rat isolated Kupffer cells （KCs） stimulated by Leptospira interrogans and Borrelia burgdorferi. METHODS： Rat Kupffer cells were separated by perfusion of the liver with 0.05% collagenase, and purified by Percoll gradients. Pudfied Kupffer cells were tested in vitro with alive L.interogans and B. burgdorferi preparations. The production of ROS was determined by chemiluminescence, whereas iNOS protein expression was evaluated by Western blot assay using anti-iNOS antibodies. RESULTS： B. burgdorferi and to a less extent L. interrogans induced ROS production with a peak 35 min after infection. The chemiluminescence signal progressively diminished and was undetectable by 180 min of incubation. Leptospirae and borreliae induced an increased iNOS expression in Kupffer cells that peaked at 6 hours and was still evident 22 h after infection. CONCLUSION： Both genera of spirochetes induced ROS and iNOS production in rat Kupffer cells. Since the cause of liver damage both in leptospiral as well as in borrelial infections are still unknown, we suggest that leptospira and borrelia damage of the liver can be initially mediated by oxygen radicals, and is then maintained at least in part by nitric oxide.

Effect of extracts from Stachys sieboldii Miq. on cellular reactive oxygen species and glutathione production and genomic DNA oxidation

Objective: To evaluate the antioxidant activity of extracts and fractions from Stachys sieboldii Miq., and to examine its effect on the cellular reactive oxygen species(ROS) and glutathione(GSH) production and genomic DNA oxidation in HT-1080 cells. Methods: The ROS generation induced by H2 O2 was measured by the dichlorofluorescein-diacetate assay. GSH levels were measured using a fluorescent method with mBBr. Genomic DNA oxidative damage was measured with levels of oxidative DNA induced by the reaction of ferritin with H2 O2. Results: The n-hexane, 85% aqueous methanol and n-butanol fractions(0.05 mg/mL concentrations) inhibited H2 O2-induced ROS generation by 63%, 35% and 45%, respectively. GSH levels were significantly increased in both acetone+methylene chloride and methanol extracts(P<0.05). Supplementation of cells with n-hexane significantly increased GSH levels at concentrations of 0.05 mg/mL(P<0.05). Both the acetone+methylene chloride and methanol extracts, as well as all fractions significantly inhibited oxidative DNA damage(P<0.05). Conclusions: These results indicate that cellular oxidation was inhibited by the n-hexane fraction and this fraction may contain valuable active compounds.

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive oxidative stress is an important characteristic that leads to the development of many cancers.Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs,which alters the growth and proliferation of ESCs and promotes their metastasis.Natural compounds,including alkaloids,terpenes,polyphenols,and xanthine compounds,can inhibit reactive oxygen species production in ESCs.These compounds reduce oxidative stress levels and subsequently inhibit the oc-currence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10,superoxide dismutase,the NF-+ACY-kappa+ADs-B/MAPK pathway,and the mammalian Nrf2/ARE target pathway.Thus,targeting tumor oxidative stress has become a key focus in anti-ESC therapy.This review discusses the potential of Natural products(NPs)for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment.The findings of this review provide a reference for drug development targeting ESCs.Nonetheless,further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Regulating Signal Pathway Triggers Circular Reactive Oxygen Species Production to Augment Oxidative Stress with Enzyme-Activated Nanoparticles

Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very challenging.Herein,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell apoptosis.The OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and DSPEPEG-GE11.OPFV-SnMP@GE11 accumulated at tumor sites through specific targeting with GE11.OPFV-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ROS.Additionally,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative stress.This strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

Natural product-induced oxidative stress-synergistic anti-tumor effects of chemotherapeutic agents

Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.

Review on reactive species in water treatment using electrical discharge plasma:formation, measurement, mechanisms and mass transfer

In the electrical discharge plasma process, various chemical and physical processes can participate in the removal of contaminants. In this paper, the chemical and physical processes that occur as a result of the electrical discharge plasma are reviewed, and their possible roles in the degradation of contaminants are discussed. Measurement methods for the quantification of important reactive species and their advantages and shortcomings are presented. Approaches on how to enhance the diffusion of the reactive species in solution are examined. In addition, the formation of typical reactive species in different electrical discharge plasma is compared.

Inflammation and reactive oxygen species in cardiovascular disease

Reactive oxygen species(ROS)have long been proposed to be mediators of experimental cardiovascular pathology.There is also a wealth of data indicating that ROS are involved in clinical cardiovascular pathology.However,multiple clinical studies have shown little benefit from anti-oxidant treatments,whereas nearly all experimental studies have shown a marked effect of anti-oxidant therapy.One reason for this discrepancy is that ROS are produced through multiple different mechanisms of which some are clinically beneficial;thus,in a defined experimental system where predominately pathological ROS are generated does not mimic a clinical setting where there are likely to be multiple ROS generating systems producing beneficial and pathological ROS.Simple inhibition of ROS would not be expected to have the same result in these two situations;ergo,it is important to understand the molecular mechanism underlying the production of ROS so that clinical treatments can be tailored to target the pathological production of ROS.One such example of this in cardiovascular biology is tissue specific inflammation-mediated ROS generation.This and the following series of articles discuss the current understanding of the role of ROS in cardiovascular disease,specifically focusing on the molecular mechanisms of ROS generation and the actions of ROS within the cardiovascular system.Although there are still many areas with regard to the effects of ROS in the cardiovascular system that are not completely understood,there is a wealth of data suggesting that blocking pathological ROS production is likely to have beneficial clinical effects compared to traditional anti-oxidants.

Light-induced ZnO/Ag/rGO bactericidal photocatalyst with synergistic effect of sustained release of silver ions and enhanced reactive oxygen species

Silver nanoparticles (Ag NPs) can effectively address the issue of antibiotic-resistant bacterial infections to reduce the potential toxicity of Ag NPs. Although challenging, it is, therefore, necessary to achieve the sustainable release of Ag+ ions from a finite amount of Ag NPs. This study aims at designing an efficient and benign antimicrobial silver-based ternary composite composed of photocatalysis zinc oxide (ZnO) and reduced graphene oxide (rGO) as a carrier, in which the reactive oxygen species (ROS) excited from ZnO and Ag+ ions released from the Ag NPs cooperate to realize an effective antibacterial activity against E. coli and S. aureus. The constant effective bacterial performance of the ternary photocatalyst with minimum Ag content can be attributed to the increase in the available quantity of ROS, which results from the enhanced separation efficiency of the photogenerated carriers. The proposed system notably realized the long-term sustainable release of Ag+ ions with low concentration for 30 days when compared with an equivalent amount of silver nitrate. Moreover, the use of the composite prevents biotoxicity and silver wastage, and imparts enhanced stability to the long-lasting antibacterial efficacy.

Cyanidin suppresses amyloid beta-induced neurotoxicity by inhibiting reactive oxygen speciesmediated DNA damage and apoptosis in PC12 cells

Amyloid beta（Aβ）-induced oxidative stress is a major pathologic hallmark of Alzheimer＇s disease. Cyanidin, a natural flavonoid compound, is neuroprotective against oxidative damage-mediated degeneration. However, its molecular mechanism remains unclear. Here, we investigated the effects of cyanidin pretreatment against Aβ-induced neurotoxicity in PC12 cells, and explored the underlying mechanisms. Cyanidin pretreatment significantly attenuated Aβ-induced cell mortality and morphological changes in PC12 cells. Mechanistically, cyanidin effectively blocked apoptosis induced by Aβ, by restoring the mitochondrial membrane potential via upregulation of Bcl-2 protein expression. Moreover, cyanidin markedly protected PC12 cells from Aβ-induced DNA damage by blocking reactive oxide species and superoxide accumulation. These results provide evidence that cyanidin suppresses Aβ-induced cytotoxicity, by preventing oxidative damage mediated by reactive oxide species, which in turn inhibits mitochondrial apoptosis. Our study demonstrates the therapeutic potential of cyanidin in the prevention of oxidative stress-mediated Aβ neurotoxicity.

Apoptotic signaling through reactive oxygen species in cancer cells

Reactive oxygen species(ROS) take part in diverse biological processes like cell growth,programmed cell death,cell senescence,and maintenance of the transformed state through regulation of signal transduction. Cancer cells adapt to new higher ROS circumstance. Sometimes,ROS induce cancer cell proliferation. Meanwhile,elevated ROS render cancer cells vulnerable to oxidative stress-induced cell death. However,this prominent character of cancer cells allows acquiring a resistance to oxidative stress conditions relative to normal cells. Activated signaling pathways that increase the level of intracellular ROS in cancer cells not only render up-regulation of several genes involved in cellular proliferation and evasion of apoptosis but also cause cancer cells and cancer stem cells to develop a high metabolic rate. In over the past several decades,many studies have indicated that ROS play a critical role as the secondary messenger of tumorigenesis and metastasis in cancer from both in vitro and in vivo. Here we summarize the role of ROS and anti-oxidants in contributing to or preventing cancer. In addition,we review the activated signaling pathways that make cancer cells susceptible to death.

The effects of reactive oxygen species in the process of skin photoaging

Skin is the largest organ of human body and it protects the organism from external stimuli.Skin will age as the organism ages in normal circumstances.Skin photoaging refers to the accumulation of ultraviolet radiation due to long-term exposure to sunlight,which results in the premature aging of skin,wrinkles,pigmentation,skin laxity,and other signs of aging.The increase in the level of reactive oxygen species(ROS)induced by ultraviolet radiation,which causes the oxidation of cells,proteins,lipids,and other components,is an important cause of accelerated photoaging of skin.For this reason,the skin's antioxidant system will further play an antioxidant role to reduce oxidative damage by inhibiting ROS production,breaking down ROS,and degrading oxides.Therefore,it is important to understand the mechanism of skin damage caused by Ultraviolet radiation,the effects of reactive oxygen species and how the body's antioxidant system exerts its antioxidant effect.This will not only deepen the understanding of skin photoaging but also provide a scientific basis for the research on how to prevent and treat photoaging.