High Levels Of Hydrogen Peroxide Research Articles

Accumulation of Hydrogen Peroxide in Flag Leaves Induces Effective Regeneration of Triticale During Rehydration After Water Stress

AbstractA key element in the effective recovery of plants after drought is slowing down of their senescence accelerated during the drought. Therefore, in this paper the relationships between hydrogen peroxide content and effective recovery during rehydration after water stress were analyzed. The study focused on two DH lines of winter triticale with different regeneration potential, as shown by different numbers of lateral stems with ears, grown during rehydration after water stress. During rehydration, the GZDH27 line grows two to three lateral stems with ears, whereas the GZDH88 line grows a single lateral stem with ear. The two DH lines of winter triticale showed comparable responses to the drought stress but their responses to rehydration after the drought stress were clearly different. Results revealed, that the increased accumulation of hydrogen peroxide, which was induced during the drought, can be maintained during rehydration, thus stimulating plant senescence. In the line GZDH88, rehydration did not slow down drought-induced senescence. This was manifested by higher levels of hydrogen peroxide, accompanied by lower levels of chlorophyll in the flag leaves of GZDH88 plants, as the result of which only one lateral stem was formed during rehydration. However, development of one lateral stems during rehydration in the GZDH88 line allowed for smaller yield loss than in the GZDH77 line, that developed of three lateral stems during rehydration. The efficient production of carbohydrates and their effective allocation into the ears of the lateral stems required considerable energy expenditure in the GZDH27 line. Our results indicate that growing three lateral stems with ears during rehydration does not guarantee limitation of grain yield loss. However, to reach the final conclusion, it is important to evaluate a greater number of triticale genotypes under drought stress and rehydration during various stages of a plants development.

Mg-ZIF nanozymes disrupt the level of ROS for osteosarcoma killing via POD activity.

Osteosarcoma (OS) is notorious for its high malignancy, and conventional chemotherapy drugs, while killing tumor cells, often inflict significant harm on the patient's body. The tumor microenvironment of OS is characterized by high levels of hydrogen peroxide (H2O2). Leveraging this feature, we have developed Mg-ZIF nanoparticles, which incorporate magnesium (Mg) to confer robust peroxidase (POD)-like enzymatic activity. These Mg-ZIF nanozymes can generate highly lethal superoxide anions within tumor cells in a responsive manner, thereby achieving effective tumor destruction. Both in vitro and in situ OS models have corroborated the anti-tumor efficacy of Mg-ZIF nanozymes, while also validating their biosafety. The design of Mg-ZIF nanozymes opens a new avenue for the treatment of OS, offering a promising therapeutic strategy.

Glutathione-depleting polyprodrug nanoparticle for enhanced photodynamic therapy and cascaded locoregional chemotherapy

Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy.

Non-proteinogenic amino acids mitigate oxidative stress and enhance the resistance of common bean plants against Sclerotinia sclerotiorum.

White mold, caused by the necrotrophic fungus Sclerotinia sclerotiorum, is a challenging disease to common bean cultivation worldwide. In the current study, two non-proteinogenic amino acids (NPAAs), γ-aminobutyric acid (GABA) and ß-alanine, were suggested as innovative environmentally acceptable alternatives for more sustainable management of white mold disease. In vitro, GABA and ß-alanine individually demonstrated potent dose-dependent fungistatic activity and effectively impeded the radial growth and development of S. sclerotiorum mycelium. Moreover, the application of GABA or ß-alanine as a seed treatment followed by three root drench applications efficiently decreased the disease severity, stimulated plant growth, and boosted the content of photosynthetic pigments of treated S. sclerotiorum-infected plants. Furthermore, although higher levels of hydrogen peroxide (H2O2), superoxide anion (O2 •-), and malondialdehyde (MDA) indicated that S. sclerotiorum infection had markedly triggered oxidative stress in infected bean plants, the exogenous application of both NPAAs significantly reduced the levels of the three studied oxidative stress indicators. Additionally, the application of GABA and ß-alanine increased the levels of both non-enzymatic (total soluble phenolics and flavonoids), as well as enzymatic (catalase [CAT], peroxidases [POX], and polyphenol oxidase [PPO]) antioxidants in the leaves of S. sclerotiorum-infected plants and improved their scavenging activity and antioxidant efficiency. Applications of GABA and ß-alanine also raised the proline and total amino acid content of infected bean plants. Lastly, the application of both NPAAs upregulated the three antioxidant-related genes PvCAT1, PvCuZnSOD1, and PvGR. Collectively, the fungistatic activity of NPAAs, coupled with their ability to alleviate oxidative stress, enhance antioxidant defenses, and stimulate plant growth, establishes them as promising eco-friendly alternatives for white mold disease management for sustainable bean production.

Kigelia africana (Lam.) Benth. fruit inhibits iron-induced lipid peroxidation and ?-amylase enzyme activity

Insufficiencies in insulin secretion and/or action cause diabetes mellitus (DM), a complex condition characterized by abnormal blood glucose levels. Diabetes is often treated by modifying either glucose metabolism, lipids metabolism, or both. A direct correlation has been found between high levels of lipid peroxide in individuals with diabetes and lower intracellular antioxidant activity. Therefore, this study was designed to investigate the effect of the aqueous extract of Kigelia africana fruit on the carbohydrate hydrolyzing enzyme, ?-amylase, and FeSO4-induced lipid peroxidation in the rat pancreas. The in vitro antioxidant potential, including assays for (1,1 diphenyl-2-picryl hydrazyl (DPPH), ferric reducing antioxidant property (FRAP), nitric oxide (NO), hydroxyl (OH) scavenging, and Fe2+ chelating abilities, of the fruit extract was also evaluated. The effect of the fruit extract on the ?-amylase enzyme, and FeSO4-induced lipid peroxidation in the rat pancreas was also evaluated. K. africana at a concentration of 0.5 mg/mL and 1 mg/mL scavenged DPPH radicals, with the lower concentration showing significant differences compared to the control. The K. africana fruit extract reduced ferric compounds significantly compared to the standard. The OH* radical scavenging results revealed that all concentrations of K. africana fruit scavenged OH* radicals without significant differences compared to the control. K. africana fruit also chelated iron significantly compared to the control. The fruit extract inhibited iron-induced lipid peroxidation in the rat pancreas and ?-amylase activity compared to the control. K. africana fruit displayed promising potential in inhibiting ?-amylase activity and associated lipid peroxidation in diabetics. Therefore, it holds strong promise for use in diabetes treatment, validating its traditional use for managing the condition.

Immunocompromisation of wheat host by L-BSO and 2,4-DPA induces susceptibility to the fungal pathogen Fusarium oxysporum

Susceptibility is defined as the disruption of host defence systems that promotes infection or limits pathogenicity. Glutathione (GSH) is a major component of defence signalling pathways that maintain redox status and is synthesised by γ-glutamyl cysteine synthetase (γ-ECS). On the other hand, lignin acts as a barrier in the primary cell wall of vascular bundles (VBs) synthesised by phenylalanine ammonia-lyase (PAL) in the intracellular system of plants. In this study, we used two inhibitors, such as L-Buthionine-sulfoximine (BSO), which irreversibly inhibits γ-ECS, and 2,4-dichlorophenoxyacetic acid (DPA), which reduces PAL activity and leads to the induction of oxidative stress in wheat (Triticum aestivum) seedlings after exposure to Fusarium oxysporum. Seedlings treated with 1 mM L-BSO and 2,4-DPA showed high levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), carbonyl (CO) content, and low activity of antioxidative enzymes [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR)] as compared to wild-type (WT) seedlings under F. oxysporum infection. Further, the content of reduced glutathione (RGSH), ascorbate (ASC), and lignin was decreased in BSO and DPA treated seedlings as compared to WT seedlings during Fusarium infection. Moreover, treatment with BSO and DPA significantly inhibited the relative activity of γ-ECS and PAL (P ≤ 0.001) in WT seedlings during Fusarium infection, which led to disintegrated VBs and, finally, cell death. Our results demonstrate that inhibition of γ-ECS and PAL by BSO and DPA, respectively, disrupts the defence mechanisms of wheat seedlings and induces susceptibility to F. oxysporum.

Impact of changes in root biomass on the occurrence of internal browning in radish root

The purpose of this study was to investigate the effects of root biomass during the later stage of growth on fatty acid composition and lipid peroxidation, and to clarify the physiological mechanisms by which these differences affect internal browning (IB) development in radish roots. Therefore, we controlled the enlargement of roots by changing the thinning period and generated plots composed of roots with different biomass in the latter half of growth. The earlier the radish seedlings were thinned, the more vigorous the root growth from an earlier stage was achieved. Earlier thinning caused IB from the early stage of root maturation, and IB severity progressed with subsequent age progression; however, IB damage did not occur when root size during the later growth stage was kept small by later thinning. Higher levels of hydrogen peroxide, peroxidase activity, NADPH-dependent reactive oxygen species (ROS) burst-related genes, and carbonyl compounds were detected in earlier-thinned large-sized roots compared to later-thinned small-sized ones. Compared with the latter small-sized roots, the former large-sized roots had a lower ratio of linoleic acid (18:2) and a higher ratio of α-linolenic acid (α-18:3). Furthermore, in earlier-thinned large-sized roots, higher levels of phospholipase- and/or lipoxygenase-related genes were detected compared to later-thinned small-sized ones. These facts suggest the possibility that root biomass in the later stage of growth affects the desaturation of membrane fatty acids, ROS concentration, and activity of fatty acid degrading enzymes, and controls the occurrence of IB injury through membrane oxidative degradation.

Abstract 4677: Characterizing resistant and metastatic phenotypes to pharmacological ascorbate in pancreatic cancer

Abstract Background and purpose: Pharmacological ascorbate (P-AscH) is a prooxidant that oxidizes to produce high levels of hydrogen peroxide. It is currently being investigated as an anti-cancer neoadjuvant for pancreatic cancer (PC). In phase I clinical trials, P-AscH has generated encouraging results in terms of efficiency and safety. However, 50% of patients do not respond to P-AscH suggesting that resistance occurs in a subset of patients. We have generated PC cell lines resistant to P-AscH to characterize mechanisms of resistance. Methodology: PANC-1 and MIA PaCa-2 PC cell lines were treated with a stepwise progression of increasing concentrations of P-AscH until 10-fold IC50 concentration was fully tolerated (AscR, ascorbate resistant) as determined by clonogenic survival. Once resistance was achieved, various redox enzyme protein expression and activity were measured to determine their role in resistance to P-AscH. Proliferation and cell cycle analysis were conducted on resistant and sensitive cells. An RNA sequencing screen was conducted as an unbiased approach to identify potential candidates crucial for resistance. Finally, phenotypes associated to increased metastatic potential, including collagen invasion and in vivo tumor colonization were explored for characterization. Results: PANC-1 and MIA PaCa-2 AscR cells developed unique mechanisms to tolerate high levels of P-AscH. PANC-1 AscR cells almost exclusively rely on catalase to detoxify H2O2 generated during P-AscH treatments, while MIA PaCa-2 AscR cells do not. It is interesting to note that not every redox enzyme was upregulated in response to P-AscH treatments, including GPx1/4. The AscR cell lines also differed in growth rates. PANC-1 AscR cells developed a faster proliferation rate, whereas MIA PaCa-2 AscR cells significantly decreased their growth. This is consistent with a shortened G1/G0 cell cycle phase and an accumulation in G2/M, respectively. The RNA sequencing screen revealed a metastatic signature in association with resistance to P-AscH, including upregulation of the PI3K/AKT axis. We observed a significant increase in collagen matrix invasion, as well as metastatic colonization in vivo. Additionally, we have observed increased expression of active AKT in both AscR cell lines, indicating a potential mechanism for the increased metastatic phenotype. Conclusion: Our findings demonstrate distinct mechanisms for AcsR cells to tolerate high doses of P-AscH. Although catalase has demonstrated to be a key factor in controlling redox flux, it may not be necessary for all cell types. Not only can P-AscH resistance alter redox enzyme expression, but we have also observed substantial increase in metastatic potential to drive invasion and tumor colonization. In summary, our data indicate a potential route for PC to tolerate high levels of P-AscH and may explain how some patients do not respond to this treatment regimen. Citation Format: Amanda N. Pope, Brianne R. O'Leary, Juan Du, Garry R. Buettner, Michael D. Henry, Joseph J. Cullen. Characterizing resistant and metastatic phenotypes to pharmacological ascorbate in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4677.

H2O2 Significantly Affects Larix kaempferi × Larix olgensis Somatic Embryogenesis.

Larch is widely distributed throughout the world and is an important species for timber supply and the extraction of industrial raw materials. In recent years, the hybrid breeding of Larix kaempferi and Larix olgensis has shown obvious heterosis in quick-growth, stress resistance and wood properties. However, its growth and development cycle is too long to meet general production needs. In order to shorten the breeding cycle, we have for the first time successfully established and optimized a somatic embryogenesis system for Larix kaempferi × Larix olgensis. We found that the highest rate of embryonal-suspensor mass (ESM) induction was observed when late cotyledonary embryos were used as explants. The induced ESMs were subjected to stable proliferation, after which abscisic acid (ABA) and polyethylene glycol (PEG) were added to successfully induce somatic embryos. Treatment with PEG and ABA was of great importance to somatic embryo formation and complemented each other's effect. ABA assisted embryo growth, whereas PEG facilitated the formation of proembryo-like structures. On top of this, we studied in more detail the relationship between redox homeostasis and the efficiency of somatic embryogenesis (frequency of ESM induction). During subculture, we observed the gradual formation of three distinct types of ESM. The Type I ESM is readily able to form somatic embryos. In contrast to type I, the type III ESM suffers from severe browning, contains a higher level of hydrogen peroxide (H2O2) and demonstrates a decreased ability to form somatic embryos. External treatment with H2O2 decreased the somatic embryogenesis efficiency of Type I and type III ESMs, or the higher the exogenous H2O2 content, the lower the resulting somatic embryogenesis efficiency. We found that treatment with the H2O2 scavenger DMTU (dimethylthiourea) could significantly increase the somatic embryogenesis efficiency of the type III ESM, as a result of a decline in endogenous H2O2 content. Overall, these findings have contributed to setting up a successful somatic embryogenesis system for larch production.

Silicon and arbuscular mycorrhizal fungi alleviate chromium toxicity in Brassica rapa by regulating Cr uptake, antioxidant defense expression, the glyoxalase system, and secondary metabolites

The potential contribution of silicon (Si) (300 mg kg−1 potash silica) or arbuscular mycorrhizal fungi (AMF) (Rhizophagus irregularis) to reduce chromium toxicity (Cr; 0 and 300 mg kg−1) in Brassica rapa was examined in this work. Under Cr stress, Si and AMF were used separately and in combination (no Si, or AMF, Si, AMF, and Si + AMF). Brassica rapa growth, colonization, photosynthesis, and physio-biochemical characteristics decreased under Cr stress. Oxidative stress was a side effect of Cr stress and was associated with high levels of methylglyoxal (MG), hydrogen peroxide (H2O2), lipid peroxidation (MDA), and maximum lipoxygenase activity (LOX). On the other hand, quantitative real-time PCR analyses of gene expression showed that under Cr stress, the expression of genes for secondary metabolites and antioxidant enzymes was higher than that under the control. The co-application of Si and AMF activated the plant defense system by improving the antioxidative enzymes activities, the potassium citrate and glutathione pool, the glyoxalase system, metabolites, and genes encoding these enzymes under Cr stress. Under the influence of Cr stress, oxidative stress was reduced by the coordinated control of the antioxidant and glyoxalase systems. However, the restricted Cr uptake and root and shoot accumulation of Si and AMF co-applied to only Cr-stressed plants was more significant. In summary, Si and AMF applied together successfully counteract the deleterious effects of Cr stress and restore growth and physio-biochemical characteristics. As a result, the beneficial effects of the combined Si and AMF application may be attributed to mycorrhizae-mediated enhanced Si absorption and metal resistance.

Lycopene modulates testicular injury oxidative stress and caspases upregulation induced by fenvalerate in male rats

Fenvalerate (FEN) is one of the widely utilized synthetic pyrethroids that may negatively impact male fertility in animals and people, while the potential mechanism is still unknown. This study aimed to assess lycopene’s potential therapeutic value in protecting male rats from testicular damage and oxidative stress caused by FEN. In our investigation, 28 male rats were randomized into four groups at random: lycopene (10 mg/kg BW), FEN (20 mg/kg BW), and lycopene plus FEN. The rats got their doses orally by gavage each day for four weeks. Animals that had consumed FEN showed high levels of hydrogen peroxide and thiobarbituric acid reactive substances, phosphatases, and aminotransferases. However, there was a considerable drop in antioxidant enzyme activity, glutathione, and protein content. Significant changes in testosterone, luteinizing and follicle-stimulating hormones, and sperm quality were also found. In addition, the expression of caspases 3 and 8 in rat testes was significantly upregulated. Biochemical, molecular, spermatological, and histological alterations have all been brought back to normal by lycopene. These findings imply that lycopene may have antioxidant and preventive properties against testicular damage brought on by FEN. Keywords: Fenvalerate; Lycopene; Apoptosis; Semen quality; Oxidative stress.

Peroxiredoxin-1 is an H2O2 safe-guard antioxidant and signalling enzyme in M1 macrophages

Macrophages are characterised by their high plasticity and ability to adapt their phenotype and functionality in response to environmental cues, resulting in a spectrum of activation states the two extremes of which are M1 and M2. Reactive oxygen species, such as hydrogen peroxide, are among the cues that impact macrophage polarisation. Moreover, high levels of hydrogen peroxide play a role in the phagocytic response executed by M1 macrophages. Therefore, macrophages must balance the need to shield themselves from the harmful effects of hydrogen peroxide bursts with the ability to interpret hydrogen peroxide signals from the surroundings and initiate a cellular response. Peroxiredoxins (PRDX) are proteins capable of performing both roles. Specifically, PRDX1 and PRDX5 have been demonstrated to safeguard macrophages against reactive oxygen species while also impacting their polarisation status. Previously conducted studies did not differentiate between the polarisation state of macrophages or investigate the signalling events triggered by PRDXs. In this study, we utilised bone marrow-derived murine macrophages polarised to the M1 and M2 states. Our findings revealed that the expression of PRDX1 was significantly higher in M1 macrophages than in M2 and unpolarised macrophages. Moreover, we present evidence that in M1 macrophages, PRDX1 interacts with ASK1, its established interaction partner, and also binds to other proteins that regulate the cellular antioxidant response. Interestingly, we found that pharmacological elevation of hydrogen peroxide levels leads to an increase in PRDX1 expression on the mRNA level, but not in the highly related PRDX2 expression. Taken together, our findings suggest that PRDX1 plays a critical role in macrophage antioxidant defence and redox signalling, and provide scope for exploring redox-signalling proteins as highly sought-after candidates for macrophage repolarisation.

Catalytic Pollutant Upgrading to Dual-Asymmetric MnO2 @polymer Nanotubes as Self-Propelled and Controlled Micromotors for H2 O2 Decomposition.

Industrial and disinfection wastewater typically contains high levels of organic pollutants and residue hydrogen peroxide, which have caused environmental concerns. In this work, dual-asymmetric MnO2 @polymer microreactors are synthesized via pollutant polymerization for self-driven and controlled H2 O2 decomposition. A hollow and asymmetric MnO2 nanotube isderived from MnO2 nanorods by selective acid etching and then coated by a polymeric layer from an aqueous phenolic pollutant via catalytic peroxymonosulfate (PMS)-induced polymerization. The evolution of particle-like polymers iscontrolled by solution pH, molar ratios of PMS/phenol, and reaction duration. The polymer-covered MnO2 tubing-structured micromotors presented a controlled motion velocity, due to the reverse torque driven by the O2 bubbles from H2 O2 decomposition in the inner tunnels. In addition, the partially coated polymeric layer can regulate the exposure and population of Mn active sites to control the H2 O2 decomposition rate, thus avoiding violent motions and massive heat caused by vigorous H2 O2 decomposition. The microreactors can maintain the function of mobility in an ultra-low H2 O2 environment (<0.31wt.%). This work provides a new strategy for the transformation of micropollutants to functional polymer-based microreactors for safe and controlled hydrogen peroxide decomposition for environmental remediation.

A tumor-microenvironment-activated nanoplatform of modified SnFe2O4 nanozyme in scaffold for enhanced PTT/PDT tumor therapy

Phototherapy has attracted widespread attention for cancer treatment due to its noninvasiveness and high selectivity. However, severe hypoxia, overexpressed glutathione and high levels of hydrogen peroxide (H2O2) of tumor microenvironment limit the antitumor efficiency of phototherapy. Herein, inspired by the specific response of nanozymes to the tumor microenvironment, a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform is constructed. In this study, tin ferrite (SnFe2O4, SFO) nanozyme as a photosensitizer was surface modified with polydopamine (denoted as P-SFO) and incorporated into poly(l-lactide) to fabricate an antitumor scaffold fabricated by selective laser sintering. On one hand, SFO nanozyme could act as a photoabsorber to convert light energy into heat for photothermal therapy (PTT). On the other hand, it played a role of photosensitizer in transferring the photon energy to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). Importantly, its multivalent metal ions redox couples would decompose H2O2 into O2 for enhancing O2-dependent PDT and consume glutathione to relieve antioxidant capability of the tumors. Besides, polydopamine as a photothermal conversion agent further enhanced the photothermal performance of SFO. The results revealed the PLLA/P-SFO scaffold possessed a photothermal conversion efficiency of 43.52% for PTT and a high ROS generation capacity of highly toxic ·O2− and ·OH for PDT. Consequently, the scaffold displayed a prominent phototherapeutic effect with antitumor rate of 96.3%. In addition, the PLLA/P-SFO scaffolds possessed good biocompatibility for cell growth. These advantages endow PLLA/P-SFO scaffold with extensive applications in biomedical fields and opened up new avenue towards nanozyme-mediated synergistic phototherapy.

Differential Responses of Antioxidant Enzymes and Lignin Metabolism in Susceptible and Resistant Sweetpotato Cultivars during Root-Knot Nematode Infection.

Root-knot nematodes (RKN) cause significant damage to sweetpotato plants and cause significant losses in yield and quality. Reactive oxygen species (ROS) play an important role in plant defenses, with levels of ROS-detoxifying antioxidant enzymes tightly regulated during pathogen infection. In this study, ROS metabolism was examined in three RKN-resistant and three RKN-susceptible sweetpotato cultivars. The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were assessed, as was lignin-related metabolism. In RKN-infected roots, both resistant and susceptible cultivars increased SOD activity to produce higher levels of hydrogen peroxide (H2O2). However, H2O2 removal by CAT activity differed between cultivars, with susceptible cultivars having higher CAT activity and lower overall H2O2 levels. In addition, the expression of phenylpropanoid-related phenylalanine ammonia-lyase and cinnamyl alcohol dehydrogenase genes, which encode enzymes involved in lignin metabolism, were higher in resistant cultivars, as were total phenolic and lignin contents. Enzyme activities and H2O2 levels were examined during the early (7 days) and late (28 days) phases of infection in representative susceptible and resistant cultivars, revealing contrasting changes in ROS levels and antioxidant responses in the different stages of infection. This study suggests that differences in antioxidant enzyme activities and ROS regulation in resistant and susceptible cultivars might explain reduced RKN infection in resistant cultivars, resulting in smaller RKN populations and overall higher resistance to infection and infestation by RKNs.

Mass Spectrometry Reveals High Levels of Hydrogen Peroxide in Pancreatic Cancer Cells

AbstractReactive oxygen species (ROS) are critical for many cellular functions, and dysregulation of ROS involves the development of multiple types of tumors, including pancreatic cancer. However, ROS have been grouped into a single biochemical entity for a long time, and the specific roles of certain types of ROS in tumor cells (e.g., pancreatic ductal adenocarcinoma (PDAC)) have not been systematically investigated. In this work, a highly sensitive and accurate mass spectrometry‐based method was applied to study PDAC cells of humans and of genetically modified animals. The results show that the oncogenic KRAS mutation promotes the accumulation of hydrogen peroxide (H2O2) rather than superoxide or hydroxyl radicals in pancreatic cancer cells. We further identified that the enriched H2O2 modifies cellular metabolites and promotes the survival of pancreatic cancer cells. These findings highlight the specific roles of H2O2 in pancreatic cancer development, which may provide new directions for pancreatic cancer therapy.

Mass Spectrometry Reveals High Levels of Hydrogen Peroxide in Pancreatic Cancer Cells.

Reactive oxygen species (ROS) are critical for many cellular functions, and dysregulation of ROS involves the development of multiple types of tumors, including pancreatic cancer. However, ROS have been grouped into a single biochemical entity for a long time, and the specific roles of certain types of ROS in tumor cells (e.g., pancreatic ductal adenocarcinoma (PDAC)) have not been systematically investigated. In this work, a highly sensitive and accurate mass spectrometry-based method was applied to study PDAC cells of humans and of genetically modified animals. The results show that the oncogenic KRAS mutation promotes the accumulation of hydrogen peroxide (H2 O2 ) rather than superoxide or hydroxyl radicals in pancreatic cancer cells. We further identified that the enriched H2 O2 modifies cellular metabolites and promotes the survival of pancreatic cancer cells. These findings highlight the specific roles of H2 O2 in pancreatic cancer development, which may provide new directions for pancreatic cancer therapy.

Responses of individual and combined polystyrene and polymethyl methacrylate nanoplastics on hormonal content, fluorescence/photochemistry of chlorophylls and ROS scavenging capacity in Lemna minor under arsenic-induced oxidative stress.

Nanoplastics alter the adverse impacts of hazardous contaminants such as heavy metals by changing their adsorption and accumulation. Few findings are available on the interaction between nanoplastic and heavy metals in plants. However, there is no report on the mechanisms for removing metal stress-mediated oxidative damage by the combination treatments of nanoplastics. To address this lack of information, polystyrene nanoplastic (PS, 100mgL-1) and polymethyl methacrylate (PMMA, 100mgL-1) were hydroponically applied to Lemna minor exposed to arsenate (As, 100μM) for 7 days. PS or PMMA caused a reduction in the contents of N, P, K, Ca, Mg and Mn, but the improved contents were detected in the presence of PS or PMMA plus As stress. The hormone contents (auxin, gibberellic acid, cytokinin, salicylic acid and jasmonic acid) reduced by stress were re-arranged through PS or PMMA applications. Based on chlorophyll efficiency, fluorescence kinetics and performance of PSII, the impaired photosynthesis by As stress was improved via PS or PMMA applications. This alleviation did not continue under the combined form of PS and PMMA in As-applied plants. All analyzed antioxidant activity (superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPX), monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR)) decreased or unchanged under As, PS or PMMA. Due to the inactivation of the defense system, L. minor had high levels of hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS), showing lipid peroxidation. After As toxicity, induvial applications of PS or PMMA indicated the activated enzyme capacity (SOD, POX, GST and GPX) and upregulated AsA/DHA, GSH/GSSG and redox state of GSH, which facilitated the removal of radical accumulation. The efficiency of the antioxidant system in As+PS+PMMA-applied L. minor was not enough to remove damage induced by As stress; hereby, TBARS and H2O2 contents were similar to the As-treated group. Our findings from alone or combined application of PS and PMMA provide new information to advance the tolerance mechanism against As exposure in L. minor.

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy.

Solid tumors have a unique tumor microenvironment (TME), which includes hypoxia, low acidity, and high hydrogen peroxide and glutathione (GSH) levels, among others. These unique factors, which offer favourable microenvironments and nourishment for tumor development and spread, also serve as a gateway for specific and successful cancer therapies. A good example is metal peroxide structures which have been synthesized and utilized to enhance oxygen supply and they have shown great promise in the alleviation of hypoxia. In a hypoxic environment, certain oxygen-dependent treatments such as photodynamic therapy and radiotherapy fail to respond and therefore modulating the hypoxic tumor microenvironment has been found to enhance the antitumor impact of certain drugs. Under acidic environments, the hydrogen peroxide produced by the reaction of metal peroxides with water not only induces oxidative stress but also produces additional oxygen. This is achieved since hydrogen peroxide acts as a reactive substrate for molecules such as catalyse enzymes, alleviating tumor hypoxia observed in the tumor microenvironment. Metal ions released in the process can also offer distinct bioactivity in their own right. Metal peroxides used in anticancer therapy are a rapidly evolving field, and there is good evidence that they are a good option for regulating the tumor microenvironment in cancer therapy. In this regard, the synthesis and mechanisms behind the successful application of metal peroxides to specifically target the tumor microenvironment are highlighted in this review. Various characteristics of TME such as angiogenesis, inflammation, hypoxia, acidity levels, and metal ion homeostasis are addressed in this regard, together with certain forms of synergistic combination treatments.

Dietary Antioxidant Curcumin Mitigates CuO Nanoparticle-Induced Cytotoxicity through the Oxidative Stress Pathway in Human Placental Cells.

The placenta is an important organ that maintains a healthy pregnancy by transporting nutrients to the fetus and removing waste from the fetus. It also acts as a barrier to protect the fetus from hazardous materials. Recent studies have indicated that nanoparticles (NPs) can cross the placental barrier and pose a health risk to the developing fetus. The high production and widespread application of copper oxide (CuO) NPs may lead to higher exposure to humans, raising concerns of health hazards, especially in vulnerable life stages, e.g., pregnancy. Oxidative stress plays a crucial role in the pathogenesis of adverse pregnancy outcomes. Due to its strong antioxidant activity, dietary curcumin can act as a therapeutic agent for adverse pregnancy. There is limited knowledge on the hazardous effects of CuO NPs during pregnancy and their mitigation by curcumin. This study aimed to investigate the preventive effect of curcumin against CuO NP-induced toxicity in human placental (BeWo) cells. CuO NPs were synthesized by a facile hydrothermal process and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and photoluminescence techniques. We observed that curcumin did not induce toxicity in BeWo cells (1-100 µg/mL for 24 h), whereas CuO NPs decreased the cell viability dose-dependently (5-200 µg/mL for 24 h). Interestingly, CuO NP-induced cytotoxicity was effectively mitigated by curcumin co-exposure. The apoptosis data also exhibited that CuO NPs modulate the expression of several genes (p53, bax, bcl-2, casp3, and casp9), the activity of enzymes (caspase-3 and -9), and mitochondrial membrane potential loss, which was successfully reverted by co-treatment with curcumin. The mechanistic study suggested that CuO-induced reactive oxygen species generation, lipid peroxidation, and higher levels of hydrogen peroxide were significantly alleviated by curcumin co-exposure. Moreover, glutathione depletion and the lower activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were effectively mitigated by curcumin. We believe this is the first report exhibiting that CuO-induced toxicity in BeWo cells can be effectively alleviated by curcumin. The pharmacological potential of dietary curcumin in NP-induced toxicity during pregnancy warrants further investigation.