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Review

Antioxidants as Modulators of NETosis: Mechanisms, Evidence, and Therapeutic Potential

by
Fabiola Zambrano
1,2,
Pamela Uribe
1,3,
Mabel Schulz
1,2,
Carlos Hermosilla
4,
Anja Taubert
4 and
Raúl Sánchez
1,2,*
1
Center of Excellence in Translational Medicine—Scientific and Technological Bioresource Nucleus (CEMT—BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile
2
Department of Preclinical Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile
3
Department of Internal Medicine, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile
4
Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(11), 5272; https://doi.org/10.3390/ijms26115272
Submission received: 22 April 2025 / Revised: 22 May 2025 / Accepted: 29 May 2025 / Published: 30 May 2025
(This article belongs to the Special Issue Antioxidants: The Molecular Guardians Against Oxidative Stress)
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Abstract

Neutrophil extracellular trap (NET) formation is a process known as NETosis and is a critical innate immune response mechanism that can become pathologically dysregulated in various inflammatory, autoimmune, infectious, and neoplastic diseases. Reactive oxygen species (ROS) play a central role in NETosis induction, making antioxidants a promising therapeutic approach. This review outlines the molecular mechanisms underlying NET formation and highlights three principal antioxidant-based inhibitory strategies: NADPH oxidase (NOX) inhibition, ROS scavenging, and myeloperoxidase (MPO) inhibition. Evidence supports the use of agents such as diphenylene iodonium (NOX inhibitor), N-acetylcysteine and glutathione (ROS scavengers), and thiocyanate (MPO inhibitor), which significantly reduce NETosis in vitro and in vivo. Moreover, natural compounds like resveratrol show pleiotropic effects by modulating neutrophil activation, ROS production, and protease activity. Combination therapies that enhance total antioxidant capacity are particularly effective, though their translation to clinical practice faces challenges such as stimulus specificity, bioavailability, and maintaining immune competence. Antioxidant-based therapies thus represent a promising avenue for targeted NETosis modulation. Future research should focus on improving delivery systems, identifying NET-specific biomarkers, and integrating antioxidants into broader immunomodulatory strategies.

1. Introduction

NETosis is a specialized form of cell death to neutrophils, a type of white blood cell crucial for innate immunity. During NETosis, neutrophils release web-like structures known as neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, to capture and neutralize pathogens [1]. While NETosis plays a vital role in host defense, it can also contribute to inflammation and tissue damage, making it a double-edged sword in immune responses [2].
NETosis can occur through different pathways, primarily categorized into “suicidal” and “vital” NETosis, depending on whether the process results in cell death [3,4]. The formation of NETs is heavily dependent on reactive oxygen species (ROS), which can be generated through NADPH oxidase (NOX) or mitochondrial pathways [5]. Autophagy, a cellular degradation process, also plays a role in regulating NETosis, influencing both pathogen clearance and inflammation [6,7].
NETs are effective in capturing and killing a wide range of pathogens, including bacteria, viruses, fungi, and protozoa, thereby preventing their spread within host tissues [2,8]. In the context of viral infections, NETs contribute to antiviral immunity but can also lead to immunopathology if not properly regulated [9]. In teleost fish, NETosis has been shown to be crucial for bacterial defense, highlighting its evolutionary conservation as an immune mechanism [7].
While NETosis is essential for pathogen defense, excessive or dysregulated NET formation is implicated in various diseases (Figure 1). NETs can contribute to the pathogenesis of conditions such as inflammatory bowel disease (IBD) [10], cancer [11], rheumatoid arthritis (RA) [12], infertility [13,14], systemic lupus erythematosus (SLE) [15], gout [16], renal diseases [17], ANCA-associated vasculitis [18], thrombosis [19], COVID-19 [20], atherosclerosis [21], small vessel vasculitis [22], type I diabetes [23], and sepsis [3], among many others, by promoting inflammation and tissue damage [3,13].
This review aims to explore how antioxidants inhibit NETosis, focusing on their mechanisms of action and antioxidant therapeutic potential. We summarize current evidence and highlight future research directions in oxidative stress related to NETs.

2. Mechanisms of ROS in NETosis Activation

ROS play a crucial role in the regulation of NETosis by inducing DNA damage and repair mechanisms. ROS can be generated through different sources.

2.1. Via NOX2 or Mitochondrial Activity

NOX2-dependent NETosis is initiated by stimuli such as phorbol esters (e.g., PMA), pathogens, or immune complexes, which activate signaling pathways (e.g., PKC or RAF-MEK-ERK) that trigger NOX assembly. NOX generates superoxide (O2−), which is converted to hydrogen peroxide (H2O2) by superoxide dismutase (SOD) [24,25]. H2O2 fuels MPO-mediated hypochlorous acid (HOCl) production, amplifying oxidative stress and causing DNA damage [26]. This recruits DNA repair proteins (e.g., APE1, PARP1) that inadvertently decondense chromatin by disrupting histone–DNA interactions, aided by NE-mediated histone cleavage and PAD4-driven citrullination [24,27]. Gasdermin D (GSDMD), a pore-forming encoded protein, forms plasma membrane pores, enabling extracellular release of chromatin decorated with antimicrobial proteins. Inhibitors like diphenylene iodonium (DPI) block NOX2, while antioxidants (e.g., catalase) scavenge H2O2, suppressing this ROS-driven suicidal NETosis pathway [3,28,29].

2.2. Via NOX-Independent NETosis

NOX-independent NETosis driven mtROS is activated by calcium ionophores (e.g., A23187), sterile injury, or UV radiation, which elevate intracellular Ca2+, triggering mitochondrial calcium uniporter (MCU) and SK3 channel activity to disrupt mitochondrial membrane potential and generate mtROS via a complex III-derived superoxide (converted to H2O2) [25,30]. This mtROS induces oxidative DNA damage, recruiting base excision repair (BER) proteins (e.g., APE1, PARP1) that decondense chromatin, while bypassing NOX2 entirely [5,25]. Unlike NOX-dependent pathways, this process is faster (~1 h), highly calcium-dependent, and suppressed by mitochondrial uncouplers (e.g., FCCP) or mtROS scavengers like MitoTEMPO [5,28,30]. It plays a role in sterile inflammation (e.g., systemic lupus erythematosus) and offers therapeutic targets such as MCU/SK3 inhibitors to mitigate NETosis without impairing antimicrobial defenses [30].

2.3. Via MPO Oxidation Pathway

The MPO oxidation pathway is critical for NETosis. MPO catalyzes the conversion of hydrogen peroxide (H2O2) to HOCl, which amplifies oxidative stress and induces DNA damage, a prerequisite for chromatin decondensation [31]. During PMA-induced NETosis, MPO cooperates with NE, and thereafter NE translocates to the nucleus to cleave histones, while MPO facilitates chromatin decondensation via ROS-mediated pathways. Pharmacological inhibition or genetic deficiency of MPO significantly reduces NET formation under these conditions, confirming its essential role [31,32]. However, MPO is dispensable in certain bacterial-induced NETosis (e.g., Pseudomonas aeruginosa), highlighting stimulus-specific mechanisms [31]. MPO also forms a redox-active complex with NE, where NADPH oxidase-derived ROS triggers NE release into the cytosol. NE then degrades F-actin to halt cytoskeletal dynamics and relocates to the nucleus, enabling DNA release [33]. MPO deficiency alters phosphatidylserine exposure and autophagy-related markers (e.g., LC3-II and p62), though without clear autophagy activation, suggesting that MPO’s role extends beyond oxidative killing to regulating cell death pathways during NETosis [32]. Thus, MPO-driven HOCl production and NE activation are pivotal in oxidative chromatin remodeling, particularly in NOX-dependent NETosis.
The mechanisms underlying NETosis, whether driven by NOX2, mitochondrial ROS, or MPO, converge on ROS-induced chromatin decondensation and extracellular release. While tightly regulated under homeostatic conditions, dysregulated NET formation contributes to the pathogenesis of numerous diseases. The stimulus-specific nature of NETosis highlights the need for targeted interventions that modulate distinct oxidative pathways. Given this, therapeutic strategies aiming to fine-tune rather than completely suppress NET formation have gained traction. The next section discusses emerging therapies that inhibit NETosis in a context-dependent manner, with evidence supporting their efficacy across autoimmune, infectious, and neoplastic diseases.

3. Evidence and Therapeutic Applications of NETosis Inhibition

NETosis dysregulation contributes to a wide spectrum of pathologies ranging from autoimmune diseases to cancer progression (Figure 1). In autoimmune and inflammatory diseases, several strategies targeting NETosis have demonstrated therapeutic promise. Therapeutic total anti-citrullinated protein antibodies (tACPAs) selectively bind citrullinated histones H2A and H4, effectively reducing NET formation in models of RA, IBD, and sepsis [34,35]. Beyond inhibiting NETosis, tACPAs promote NET clearance by macrophages, underscoring their dual anti-inflammatory and pro-resolving effects [35]. This targeted approach offers a potentially disease-modifying immunotherapy with minimal systemic immunosuppression. Similarly, inhibition of protein arginine deiminase 4 (PAD4), a key enzyme mediating histone citrullination, is effective in models of SLE and septic shock [36]. PAD4 inhibitors like Cl-amidine, BB-Cl-amidine, and GSK484 not only suppress NET formation but also attenuate ovarian cancer metastasis, pointing to PAD4 as a central player in NET-driven pathologies [37]. Complementing these strategies, DNase I-based therapies degrade the extracellular DNA backbone of NETs, alleviating synovial inflammation and enhancing the efficacy of anti-PD-1 immunotherapy in colorectal cancer [38]. Notably, nanoparticle-encapsulated DNase I offers targeted delivery, preserving immune function while significantly reducing breast cancer lung metastases [39]. In acne vulgaris, Propionibacterium acnes induces NET formation, contributing to cutaneous inflammation. Inhibition of the NLRP3 inflammasome effectively reduces NETosis in murine models, while MPO inhibitors such as thiocyanate and selenocyanate prevent NET-mediated tissue injury [40,41,42]. These findings highlight the potential of oxidative stress modulators in treating inflammatory skin disorders and reposition dermatological therapeutics as NET-targeting agents.
In the context of cancer therapy resistance, NETs can physically entrap chemotherapeutic agents such as doxorubicin, reducing their availability and efficacy in the tumor microenvironment [43]. This ‘physical resistance’ mechanism has been observed in models of multiple myeloma and bladder cancer, where DNase I treatment restores drug penetration and enhances therapeutic response [39,43]. Similarly, NETs form a barrier against ionizing radiation and cytotoxic immune cells, shielding tumor cells from both radiotherapy and immunotherapy [37,39]. Inhibitors of NE, including BAY 85-8501, as well as DNase I, have been shown to disrupt these protective networks, thereby sensitizing tumors to radiation and enhancing the efficacy of immune checkpoint inhibitors targeting PD-1 and CTLA-4 in colorectal and pancreatic cancers [38].
Among the diverse strategies targeting NETosis, antioxidant compounds have gained particular interest due to their ability to modulate ROS-dependent pathways central to NET formation. The following section explores the mechanistic basis and therapeutic potential of antioxidants as NETosis inhibitors across various pathological contexts.

4. Antioxidants as NETosis Inhibitors

NETosis plays a dual role in host defense and pathological inflammation, driving interest in antioxidant strategies to modulate this process. Research highlights several enzymatic and non-enzymatic antioxidants that effectively inhibit NETosis through diverse mechanisms, particularly by targeting ROS and associated pathways [44,45]. Although direct studies on enzymes like superoxide dismutase (SOD) and catalase are limited, it is plausible to assume that their natural function in neutralizing superoxide and hydrogen peroxide contributes significantly to maintaining redox balance and preventing excessive NET release [28]. The inhibition of NOX by compounds such as DPI and metformin suggests that reducing ROS at the source can effectively disrupt the NETosis cascade [46]. Similarly, the inhibition of MPO by thiocyanate and selenocyanate not only prevents HOCl formation but may also attenuate the downstream tissue damage associated with chronic inflammation [45]. Natural antioxidant like resveratrol has shown multifaceted effects, suppressing MPO and elastase activity, modulating ROS levels, and altering neutrophil behavior, which indicates their therapeutic potential beyond general antioxidative functions [47]. This antioxidant inhibits NETosis through multiple molecular mechanisms that converge on key signaling pathways. Resveratrol has been shown to suppress the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of inflammatory gene expression [48]. By inhibiting NF-κB signaling, resveratrol reduces the transcription of pro-inflammatory cytokines and chemokines that contribute to neutrophil priming and NET formation. In addition, they attenuate ROS production. Furthermore, this polyphenol interferes with upstream kinase cascades involved in NETosis initiation, notably the PI3K (phosphoinositide 3-kinase) and MAPK (mitogen-activated protein kinase) pathways. Through the modulation of these signaling routes, resveratrol effectively dampens neutrophil activation and impair the downstream processes required for chromatin decondensation and extracellular trap release [49]. The synergistic actions of thiol-based compounds, like NAC with glutathione, and vitamins C and E in abolishing NET formation further support the idea that restoring cellular redox homeostasis could be a central strategy to control pathological NETosis [44]. Overall, while more targeted studies are needed, the current evidence supports the conjecture that antioxidant-based therapies may represent a promising avenue for mitigating NET-associated inflammatory tissue damage. Table 1 provides a summary of the main compound with antioxidants activity investigated for their inhibitory effects on NETosis, detailing their mechanisms of action and impact on the process.
NETosis inhibition is achieved by compounds with antioxidant activity, with three main molecular targets offering distinct yet complementary strategies: NOX inhibition, ROS scavenging, and MPO inhibition [44,45]. The NOX inhibition pathway targets the enzymatic production of superoxide (O2−), a key driver of NET formation in many stimuli. Inhibitors like DPI robustly block both spontaneous and PMA-induced NETosis by halting superoxide generation [45]. Similarly, apocynin disrupts NOX complex assembly, reducing NETs particularly in infectious parasite models such as Leishmania [60]. While effective, this approach carries a major caveat: broad NOX inhibition can compromise host antimicrobial defenses, potentially increasing infection susceptibility [60]. On the other hand, ROS scavenging neutralizes excessive ROS production, restoring intracellular redox balance and preventing NET-associated tissue injury. Molecules like N-acetylcysteine (NAC) and glutathione (GSH) reduce NETosis, mitigating reactive nitrogen species (RNS) levels [24,44]. Catalase, which directly scavenges H2O2—a potent NETosis trigger—shows superior efficacy compared to superoxide dismutase (SOD) [45,61]. Additionally, combined antioxidant therapies (e.g., vitamin C/E + GSH) synergistically enhance suppression of LPS-induced NETs, outperforming monotherapies [44]. Finally, MPO specific inhibition interferes with the downstream formation of HOCl, a cytotoxic oxidant essential for chromatin decondensation in NETosis [45]. Inhibitors such as 4-ABAH and thiocyanate effectively block HOCl production, reducing NET release in PMA- and HOCl-induced settings. However, MPO inhibition exhibits context specificity—being ineffective against NETosis triggered by Leishmania or calcium ionophores, which activate MPO-independent pathways [45,60].
Taken together, these three pathways offer a rational framework for targeted NETosis modulation (Figure 2). NOX inhibitors with MPO blockers show enhanced efficacy, especially in ROS-dependent NETosis [44]. Nevertheless, a critical therapeutic balance must be maintained: while suppression of pathological NETs is desirable, complete NETosis inhibition may impair innate immunity. Thus, future strategies must aim for selective, context-specific modulation to mitigate NET-driven pro-inflammatory pathology without compromising host defense.

5. Synergistic Strategies: Antioxidants in Combination Therapies

A recent study highlighted the potential of combinatorial approaches that integrate antioxidants with enzymatic NET-disrupting agents to achieve superior therapeutic outcomes. The concomitant use of GSH and NAC significantly enhanced inhibitory effects on NET formation compared to the administration of either compound alone, by a synergistic interplay in mitigating oxidative stress [44]. While DNase I enzymatically degrades the DNA backbone of pre-formed NETs, antioxidants such as GSH and NAC act upstream by neutralizing ROS, thereby preventing the initiation of NETosis [44]. Furthermore, DNase I primarily attenuates the late-phase oxidative burst, whereas antioxidants target early ROS generation, collectively providing a more comprehensive blockade of NET formation [62]. These findings underscore the therapeutic relevance of combining antioxidants with NET-targeting agents to disrupt both the formation and persistence of NETs in inflammatory pathologies.
In parallel, preclinical studies have demonstrated the therapeutic benefit of combining DNase I with conventional antibiotic regimens. In a murine model of abdominal sepsis, the co-administration of DNase I and antibiotics markedly reduced systemic inflammation, tissue damage, and mortality, outperforming the effects observed with either treatment alone [63]. Notably, spectral analysis revealed a significant reduction in Gram-negative bacterial load following the combined intervention, suggesting enhanced bacterial clearance [63]. Furthermore, this synergistic strategy led to a substantial decrease in both the number of bacterial colony-forming units (CFUs) and overall microbial diversity, with the most pronounced effects observed when antibiotics were administered in conjunction with DNase I [63]. These findings support the concept that dismantling the NET scaffold enhances antimicrobial penetration and efficacy, positioning DNase I-antibiotic combinations as a promising approach to overcome infection persistence associated with NET-mediated bacterial protection.

6. Challenges and Future Directions

Although antioxidant-based strategies to modulate NETosis have shown promise in preclinical models, their translation into effective clinical or veterinary applications remains complex. To date, no clinical trials directly assessing antioxidants as NETosis inhibitors in humans have been reported. Available evidence is largely limited to ex vivo studies using isolated human neutrophils and in vivo preclinical models—such as murine models of gout, sepsis, and autoimmune disease. These findings provide strong mechanistic support, but the absence of clinical data underscores the need for translational research efforts, including early-phase human trials, to determine safety, efficacy, and therapeutic relevance in NET-associated pathologies. One of the primary challenges lies in the stimulus-dependent variability of NETosis pathways, where certain triggers induce ROS-dependent mechanisms while others proceed via ROS-independent routes. This mechanistic heterogeneity complicates the selection of universally effective antioxidants. Furthermore, many compounds that demonstrate strong in vitro efficacy often fail in vivo due to poor bioavailability, rapid metabolism, and limited tissue targeting—highlighting that dosing and pharmacokinetics are critical factors for successful translational application.
An additional concern in the use of antioxidants is their long-term use. While antioxidants are vital for neutralizing excess free radicals, long-term supplementation, particularly at pharmacological doses, disrupts immune function, increases infection/cancer risks, and may worsen redox balance. The risk of immune suppression is another concern, given that while excessive NET formation contributes to tissue damage and chronic inflammation, NETs also serve vital antimicrobial functions. Therefore, any therapeutic strategy must strike a delicate balance between dampening pathological NETosis and preserving host defense.
To overcome these limitations, future research should focus on the development of targeted delivery systems (e.g., nanoparticles, prodrugs) that enhance the tissue-specific action of antioxidants while minimizing systemic effects. Equally important is the identification of reliable biomarkers capable of differentiating between physiological and pathological NET formation. These biomarkers could guide the implementation of precision therapies and enable real-time monitoring of treatment efficacy. Finally, large-scale, well-controlled clinical studies are essential to establish safety profiles, therapeutic windows, and long-term outcomes of antioxidant-based NETosis modulation.

7. Conclusions

NETosis has emerged as a key immunopathological mechanism involved in a wide range of diseases, including chronic inflammation, infection, cancer, and reproductive dysfunction. Given the central role of oxidative stress in NET formation, antioxidants—both enzymatic and non-enzymatic—have been extensively studied as potential modulators. This review highlighted the mechanisms by which agents such as DPI, NAC, resveratrol, and glutathione interfere with NETosis through ROS scavenging, NOX inhibition, and MPO suppression, leading to reduced tissue damage in various disease models.
Moreover, emerging evidence suggests that combinatorial therapies—integrating antioxidants with agents like DNase I—may offer superior outcomes by targeting both the initiation and persistence phases of NET formation. However, clinical translation continues to face key challenges, including pathway heterogeneity, limited pharmacokinetic stability of antioxidants, and the necessity to maintain innate immune competence.
In summary, antioxidant-based NETosis inhibition holds considerable therapeutic promise, but its clinical application requires further refinement through targeted delivery technologies, biomarker-driven patient stratification, and rigorous translational research. Addressing these challenges will be critical to advancing this strategy from bench to bedside.

Author Contributions

F.Z., P.U., M.S., R.S., C.H. and A.T. wrote and reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Fondo Nacional de Investigación Científica y Tecnológica (ANID/FONDECYT), Chile (grant number 1230410 to R.S.). Also, we would like to express our gratitude to ANID FONDEQUIP EQM200228. Finally, this research was funded partially by the Universidad de La Frontera, for sponsoring teachers’ support, grant PP24–0008.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Brinkmann, V.; Reichard, U.; Goosmann, C.; Fauler, B.; Uhlemann, Y.; Weiss, D.S.; Weinrauch, Y.; Zychlinsky, A. Neutrophil extracellular traps kill bacteria. Science 2004, 303, 1532–1535. [Google Scholar] [CrossRef] [PubMed]
  2. Thiam, H.R.; Wong, S.L.; Wagner, D.D.; Waterman, C.M. Cellular Mechanisms of NETosis. Annu. Rev. Cell Dev. Biol. 2020, 36, 191–218. [Google Scholar] [CrossRef]
  3. Huang, J.; Hong, W.; Wan, M.; Zheng, L. Molecular mechanisms and therapeutic target of NETosis in diseases. MedComm (2020) 2022, 3, e162. [Google Scholar] [CrossRef] [PubMed]
  4. Yipp, B.G.; Kubes, P. NETosis: How vital is it? Blood 2013, 122, 2784–2794. [Google Scholar] [CrossRef] [PubMed]
  5. Azzouz, D.; Palaniyar, N. How Do ROS Induce NETosis? Oxidative DNA Damage, DNA Repair, and Chromatin Decondensation. Biomolecules 2024, 14, 1307. [Google Scholar] [CrossRef]
  6. Liang, X.; Liu, L.; Wang, Y.; Guo, H.; Fan, H.; Zhang, C.; Hou, L.; Liu, Z. Autophagy-driven NETosis is a double-edged—Review. Biomed. Pharmacother. 2020, 126, 110065. [Google Scholar] [CrossRef]
  7. Cao, J.F.; Chen, J. Pseudomonas plecoglossicida infection induces neutrophil autophagy-driven NETosis in large yellow croaker Larimichthys crocea. Front. Immunol. 2024, 15, 1521080. [Google Scholar] [CrossRef]
  8. Burgener, S.S.; Schroder, K. Neutrophil Extracellular Traps in Host Defense. Cold Spring Harb. Perspect. Biol. 2020, 12, a037028. [Google Scholar] [CrossRef]
  9. Schonrich, G.; Raftery, M.J. Neutrophil Extracellular Traps Go Viral. Front. Immunol. 2016, 7, 366. [Google Scholar] [CrossRef]
  10. Dos Santos Ramos, A.; Viana, G.C.S.; de Macedo Brigido, M.; Almeida, J.F. Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets. Pharmacol. Res. 2021, 171, 105779. [Google Scholar] [CrossRef]
  11. Liang, Y.; Wu, G.; Tan, J.; Xiao, X.; Yang, L.; Saw, P.E. Targeting NETosis: Nature’s alarm system in cancer progression. Cancer Drug Resist. 2024, 7, 28. [Google Scholar] [CrossRef] [PubMed]
  12. Shu, Y.; Yang, R.; Wen, H.; Dong, Q.; Chen, Z.; Xiang, Y.; Wu, H. Myricetin reduces neutrophil extracellular trap release in a rat model of rheumatoid arthritis, which is associated with a decrease in disease severity. Innate Immun. 2024, 30, 66–78. [Google Scholar] [CrossRef] [PubMed]
  13. Schulz, M.; Zambrano, F.; Schuppe, H.C.; Wagenlehner, F.; Taubert, A.; Ulrich, G.; Sanchez, R.; Hermosilla, C. Determination of leucocyte extracellular traps (ETs) in seminal fluid (ex vivo) in infertile patients-A pilot study. Andrologia 2019, 51, e13356. [Google Scholar] [CrossRef] [PubMed]
  14. Zambrano, F.; Carrau, T.; Gartner, U.; Seipp, A.; Taubert, A.; Felmer, R.; Sanchez, R.; Hermosilla, C. Leukocytes coincubated with human sperm trigger classic neutrophil extracellular traps formation, reducing sperm motility. Fertil. Steril. 2016, 106, 1053–1060.e1. [Google Scholar] [CrossRef]
  15. Wang, M.; Ishikawa, T.; Lai, Y.; Nallapothula, D.; Singh, R.R. Diverse Roles of NETosis in the Pathogenesis of Lupus. Front. Immunol. 2022, 13, 895216. [Google Scholar] [CrossRef]
  16. Liu, L.; Shan, L.; Wang, H.; Schauer, C.; Schoen, J.; Zhu, L.; Lu, C.; Wang, Z.; Xue, Y.; Wu, H.; et al. Neutrophil Extracellular Trap-Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout. Arthritis Rheumatol. 2023, 75, 1039–1047. [Google Scholar] [CrossRef]
  17. Salazar-Gonzalez, H.; Zepeda-Hernandez, A.; Melo, Z.; Saavedra-Mayorga, D.E.; Echavarria, R. Neutrophil Extracellular Traps in the Establishment and Progression of Renal Diseases. Medicina 2019, 55, 431. [Google Scholar] [CrossRef]
  18. Ge, S.; Zhu, X.; Xu, Q.; Wang, J.; An, C.; Hu, Y.; Yang, F.; Wang, X.; Yang, Y.; Chen, S.; et al. Neutrophils in ANCA-associated vasculitis: Mechanisms and implications for management. Front. Pharmacol. 2022, 13, 957660. [Google Scholar] [CrossRef]
  19. Martinod, K.; Wagner, D.D. Thrombosis: Tangled up in NETs. Blood 2014, 123, 2768–2776. [Google Scholar] [CrossRef]
  20. Serrano-Gonzalo, I.; Menendez-Jandula, B.; Franco-Garcia, E.; Arevalo-Vargas, I.; Lahoz-Gil, C.; Latre, P.; Roca-Esteve, S.; Kohler, R.; Lopez de Frutos, L.; Giraldo, P. Neutrophil extracellular traps and macrophage activation contibute to thrombosis and post-covid syndrome in SARS-CoV-2 infection. Front. Immunol. 2025, 16, 1507167. [Google Scholar] [CrossRef]
  21. Yalcinkaya, M.; Fotakis, P.; Liu, W.; Endo-Umeda, K.; Dou, H.; Abramowicz, S.; Xiao, T.; Libby, P.; Wang, N.; Tall, A.R.; et al. Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1beta secretion. Cardiovasc. Res. 2023, 119, 969–981. [Google Scholar] [CrossRef] [PubMed]
  22. Safi, R.; Kallas, R.; Bardawil, T.; Mehanna, C.J.; Abbas, O.; Hamam, R.; Uthman, I.; Kibbi, A.G.; Nassar, D. Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behcet’s disease. J. Dermatol. Sci. 2018, 92, 143–150. [Google Scholar] [CrossRef] [PubMed]
  23. Petrelli, A.; Popp, S.K.; Fukuda, R.; Parish, C.R.; Bosi, E.; Simeonovic, C.J. The Contribution of Neutrophils and NETs to the Development of Type 1 Diabetes. Front. Immunol. 2022, 13, 930553. [Google Scholar] [CrossRef] [PubMed]
  24. Azzouz, D.; Palaniyar, N. ROS and DNA repair in spontaneous versus agonist-induced NETosis: Context matters. Front. Immunol. 2022, 13, 1033815. [Google Scholar] [CrossRef]
  25. Azzouz, D.; Palaniyar, N. Mitochondrial ROS and base excision repair steps leading to DNA nick formation drive ultraviolet induced-NETosis. Front. Immunol. 2023, 14, 1198716. [Google Scholar] [CrossRef]
  26. Donkel, S.J.; Wolters, F.J.; Ikram, M.A.; de Maat, M.P.M. Circulating Myeloperoxidase (MPO)-DNA complexes as marker for Neutrophil Extracellular Traps (NETs) levels and the association with cardiovascular risk factors in the general population. PLoS ONE 2021, 16, e0253698. [Google Scholar] [CrossRef]
  27. Hu, Z.; Hua, X.; Mo, X.; Chang, Y.; Chen, X.; Xu, Z.; Tao, M.; Hu, G.; Song, J. Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis. iScience 2023, 26, 107162. [Google Scholar] [CrossRef]
  28. Vorobjeva, N.V.; Chernyak, B.V. NETosis: Molecular Mechanisms, Role in Physiology and Pathology. Biochemistry 2020, 85, 1178–1190. [Google Scholar] [CrossRef]
  29. Moran, G.; Uberti, B.; Quiroga, J. Role of Cellular Metabolism in the Formation of Neutrophil Extracellular Traps in Airway Diseases. Front. Immunol. 2022, 13, 850416. [Google Scholar] [CrossRef]
  30. Douda, D.N.; Khan, M.A.; Grasemann, H.; Palaniyar, N. SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx. Proc. Natl. Acad. Sci. USA 2015, 112, 2817–2822. [Google Scholar] [CrossRef]
  31. Parker, H.; Winterbourn, C.C. Reactive oxidants and myeloperoxidase and their involvement in neutrophil extracellular traps. Front. Immunol. 2012, 3, 424. [Google Scholar] [CrossRef] [PubMed]
  32. Kremserova, S.; Kocurkova, A.; Chorvatova, M.; Klinke, A.; Kubala, L. Myeloperoxidase Deficiency Alters the Process of the Regulated Cell Death of Polymorphonuclear Neutrophils. Front. Immunol. 2022, 13, 707085. [Google Scholar] [CrossRef]
  33. Metzler, K.D.; Goosmann, C.; Lubojemska, A.; Zychlinsky, A.; Papayannopoulos, V. A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell Rep. 2014, 8, 883–896. [Google Scholar] [CrossRef] [PubMed]
  34. Khandpur, R.; Carmona-Rivera, C.; Vivekanandan-Giri, A.; Gizinski, A.; Yalavarthi, S.; Knight, J.S.; Friday, S.; Li, S.; Patel, R.M.; Subramanian, V.; et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci. Transl. Med. 2013, 5, 178ra140. [Google Scholar] [CrossRef] [PubMed]
  35. Chirivi, R.G.S.; van Rosmalen, J.W.G.; van der Linden, M.; Euler, M.; Schmets, G.; Bogatkevich, G.; Kambas, K.; Hahn, J.; Braster, Q.; Soehnlein, O.; et al. Therapeutic ACPA inhibits NET formation: A potential therapy for neutrophil-mediated inflammatory diseases. Cell Mol. Immunol. 2021, 18, 1528–1544. [Google Scholar] [CrossRef]
  36. Li, X.; Xiao, S.; Filipczak, N.; Yalamarty, S.S.K.; Shang, H.; Zhang, J.; Zheng, Q. Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation. Int. J. Nanomed. 2023, 18, 5265–5287. [Google Scholar] [CrossRef]
  37. Jaboury, S.; Wang, K.; O’Sullivan, K.M.; Ooi, J.D.; Ho, G.Y. NETosis as an oncologic therapeutic target: A mini review. Front. Immunol. 2023, 14, 1170603. [Google Scholar] [CrossRef]
  38. Yan, M.; Gu, Y.; Sun, H.; Ge, Q. Neutrophil extracellular traps in tumor progression and immunotherapy. Front. Immunol. 2023, 14, 1135086. [Google Scholar] [CrossRef]
  39. Xu, X.; Wang, X.; Zheng, Z.; Guo, Y.; He, G.; Wang, Y.; Fu, S.; Zheng, C.; Deng, X. Neutrophil Extracellular Traps in Breast Cancer: Roles in Metastasis and Beyond. J. Cancer 2024, 15, 3272–3283. [Google Scholar] [CrossRef]
  40. Kim, H.J.; Lee, Y.S.; Lee, B.S.; Han, C.H.; Kim, S.G.; Kim, C.H. NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: Implications of NETosis inhibition for acne skin inflammation treatment. Cell Mol. Immunol. 2024, 21, 466–478. [Google Scholar] [CrossRef]
  41. Chen, X.; Cuffari, B.J.; Dubljevic, V.; Shirali, A.; Zhou, J.; Campbell, J.A.; Suits, S.C.; O’Sullivan, K.M.; Hansen, J.E. Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody. Immunohorizons 2022, 6, 356–365. [Google Scholar] [CrossRef] [PubMed]
  42. Chamardani, T.M.; Amiritavassoli, S. Inhibition of NETosis for treatment purposes: Friend or foe? Mol. Cell Biochem. 2022, 477, 673–688. [Google Scholar] [CrossRef] [PubMed]
  43. Shahzad, M.H.; Feng, L.; Su, X.; Brassard, A.; Dhoparee-Doomah, I.; Ferri, L.E.; Spicer, J.D.; Cools-Lartigue, J.J. Neutrophil Extracellular Traps in Cancer Therapy Resistance. Cancers 2022, 14, 1359. [Google Scholar] [CrossRef] [PubMed]
  44. Munoz-Sanchez, G.; Godinez-Mendez, L.A.; Fafutis-Morris, M.; Delgado-Rizo, V. Effect of Antioxidant Supplementation on NET Formation Induced by LPS In Vitro; the Roles of Vitamins E and C, Glutathione, and N-acetyl Cysteine. Int. J. Mol. Sci. 2023, 24, 13162. [Google Scholar] [CrossRef]
  45. Hallberg, L.A.E.; Barlous, K.; Hawkins, C.L. Antioxidant Strategies to Modulate NETosis and the Release of Neutrophil Extracellular Traps during Chronic Inflammation. Antioxidants 2023, 12, 478. [Google Scholar] [CrossRef]
  46. Menegazzo, L.; Scattolini, V.; Cappellari, R.; Bonora, B.M.; Albiero, M.; Bortolozzi, M.; Romanato, F.; Ceolotto, G.; Vigili de Kreutzeberg, S.; Avogaro, A.; et al. The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo. Acta Diabetol. 2018, 55, 593–601. [Google Scholar] [CrossRef]
  47. Ohinata, H.; Phimarn, W.; Mizuno, M.; Obama, T.; Fukuhara, K.; Makiyama, T.; Watanabe, Y.; Itabe, H. Suppressive effect of resveratrol, catechin and their conformationally constrained analogs on neutrophil extracellular trap formation by HL-60-derived neutrophils. J. Clin. Biochem. Nutr. 2024, 75, 17–23. [Google Scholar] [CrossRef]
  48. Bilski, R.; Nuszkiewicz, J. Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes. Int. J. Mol. Sci. 2025, 26, 2873. [Google Scholar] [CrossRef]
  49. de Souza Andrade, M.M.; Leal, V.N.C.; Fernandes, I.G.; Gozzi-Silva, S.C.; Beserra, D.R.; Oliveira, E.A.; Teixeira, F.M.E.; Yendo, T.M.; Sousa, M.; Teodoro, W.R.; et al. Resveratrol Downmodulates Neutrophil Extracellular Trap (NET) Generation by Neutrophils in Patients with Severe COVID-19. Antioxidants 2022, 11, 1690. [Google Scholar] [CrossRef]
  50. Vorobjeva, N.V.; Pinegin, B.V. Effects of the antioxidants Trolox, Tiron and Tempol on neutrophil extracellular trap formation. Immunobiology 2016, 221, 208–219. [Google Scholar] [CrossRef]
  51. Bekeschus, S.; Winterbourn, C.C.; Kolata, J.; Masur, K.; Hasse, S.; Broker, B.M.; Parker, H.A. Neutrophil extracellular trap formation is elicited in response to cold physical plasma. J. Leukoc. Biol. 2016, 100, 791–799. [Google Scholar] [CrossRef] [PubMed]
  52. Wang, C.; Xia, W. Proanthocyanidin Regulates NETosis and Inhibits the Growth and Proliferation of Liver Cancer Cells—In Vivo, In Vitro and In Silico Investigation. Cell Biochem. Biophys. 2025, 83, 1223–1235. [Google Scholar] [CrossRef] [PubMed]
  53. Schorn, C.; Janko, C.; Krenn, V.; Zhao, Y.; Munoz, L.E.; Schett, G.; Herrmann, M. Bonding the foe—NETting neutrophils immobilize the pro-inflammatory monosodium urate crystals. Front. Immunol. 2012, 3, 376. [Google Scholar] [CrossRef] [PubMed]
  54. Chen, J.; Wang, T.; Li, X.; Gao, L.; Wang, K.; Cheng, M.; Zeng, Z.; Chen, L.; Shen, Y.; Wen, F. DNA of neutrophil extracellular traps promote NF-kappaB-dependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease. Signal Transduct. Target. Ther. 2024, 9, 163. [Google Scholar] [CrossRef]
  55. Leung, H.H.L.; Perdomo, J.; Ahmadi, Z.; Yan, F.; McKenzie, S.E.; Chong, B.H. Inhibition of NADPH oxidase blocks NETosis and reduces thrombosis in heparin-induced thrombocytopenia. Blood Adv. 2021, 5, 5439–5451. [Google Scholar] [CrossRef]
  56. Almasi, N.; Torok, S.; Al-Awar, A.; Veszelka, M.; Kiraly, L.; Borzsei, D.; Szabo, R.; Varga, C. Voluntary Exercise-Mediated Protection in TNBS-Induced Rat Colitis: The Involvement of NETosis and Prdx Antioxidants. Antioxidants 2023, 12, 1531. [Google Scholar] [CrossRef]
  57. Chen, H.; Xu, X.; Tang, Q.; Ni, L.; Cao, S.; Hao, Y.; Wang, L.; Hu, X. (+)-Borneol inhibits the generation of reactive oxygen species and neutrophil extracellular traps induced by phorbol-12-myristate-13-acetate. Front. Pharmacol. 2022, 13, 1023450. [Google Scholar] [CrossRef]
  58. Khan, M.A.; D’Ovidio, A.; Tran, H.; Palaniyar, N. Anthracyclines Suppress Both NADPH Oxidase- Dependent and -Independent NETosis in Human Neutrophils. Cancers 2019, 11, 1328. [Google Scholar] [CrossRef]
  59. Dodo, K.; Kuboki, E.; Shimizu, T.; Imamura, R.; Magarisawa, M.; Takahashi, M.; Tokuhiro, T.; Yotsumoto, S.; Asano, K.; Nakao, S.; et al. Development of a Water-Soluble Indolylmaleimide Derivative IM-93 Showing Dual Inhibition of Ferroptosis and NETosis. ACS Med. Chem. Lett. 2019, 10, 1272–1278. [Google Scholar] [CrossRef]
  60. Rochael, N.C.; Guimaraes-Costa, A.B.; Nascimento, M.T.; DeSouza-Vieira, T.S.; Oliveira, M.P.; Garcia e Souza, L.F.; Oliveira, M.F.; Saraiva, E.M. Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites. Sci. Rep. 2015, 5, 18302. [Google Scholar] [CrossRef]
  61. Remijsen, Q.; Kuijpers, T.W.; Wirawan, E.; Lippens, S.; Vandenabeele, P.; Vanden Berghe, T. Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality. Cell Death Differ. 2011, 18, 581–588. [Google Scholar] [CrossRef] [PubMed]
  62. Munafo, D.B.; Johnson, J.L.; Brzezinska, A.A.; Ellis, B.A.; Wood, M.R.; Catz, S.D. DNase I inhibits a late phase of reactive oxygen species production in neutrophils. J. Innate Immun. 2009, 1, 527–542. [Google Scholar] [CrossRef] [PubMed]
  63. Willemsen, J.F.; Wenskus, J.; Lenz, M.; Rhode, H.; Trochimiuk, M.; Appl, B.; Pagarol-Raluy, L.; Bornigen, D.; Bang, C.; Reinshagen, K.; et al. DNases improve effectiveness of antibiotic treatment in murine polymicrobial sepsis. Front. Immunol. 2023, 14, 1254838. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Pathologies associated with NETosis. Schematic overview of major human diseases in which neutrophil extracellular traps (NETs) contribute to pathogenesis through mechanisms such as tissue damage, immune activation, thrombosis, and impaired healing. Examples include autoimmune, infectious, inflammatory, metabolic, and reproductive disorders. Created with BioRender.com.
Figure 1. Pathologies associated with NETosis. Schematic overview of major human diseases in which neutrophil extracellular traps (NETs) contribute to pathogenesis through mechanisms such as tissue damage, immune activation, thrombosis, and impaired healing. Examples include autoimmune, infectious, inflammatory, metabolic, and reproductive disorders. Created with BioRender.com.
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Figure 2. Inhibition of NETosis by antioxidants and the molecular pathways involved. The activation of neutrophil extracellular trap (NET) formation is triggered by microbial pathogens, pro-inflammatory cytokines, and oxidative stress, primarily mediated through NADPH oxidase-derived reactive oxygen species (ROS). This cascade promotes DNA decondensation and the release of NETs, a process facilitated by key enzymes such as myeloperoxidase (MPO), neutrophil elastase (NE), and peptidylarginine deiminase 4 (PAD4). Antioxidants inhibit NETosis by targeting critical signaling pathways, including direct ROS scavenging, inhibition of NADPH oxidase, and suppression of MPO activity. This multi-level interference leads to a reduction in tissue damage and contributes to protection against NET-associated diseases. Created with BioRender.com.
Figure 2. Inhibition of NETosis by antioxidants and the molecular pathways involved. The activation of neutrophil extracellular trap (NET) formation is triggered by microbial pathogens, pro-inflammatory cytokines, and oxidative stress, primarily mediated through NADPH oxidase-derived reactive oxygen species (ROS). This cascade promotes DNA decondensation and the release of NETs, a process facilitated by key enzymes such as myeloperoxidase (MPO), neutrophil elastase (NE), and peptidylarginine deiminase 4 (PAD4). Antioxidants inhibit NETosis by targeting critical signaling pathways, including direct ROS scavenging, inhibition of NADPH oxidase, and suppression of MPO activity. This multi-level interference leads to a reduction in tissue damage and contributes to protection against NET-associated diseases. Created with BioRender.com.
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Table 1. Summary of compounds with antioxidant activity shown to suppress NETosis.
Table 1. Summary of compounds with antioxidant activity shown to suppress NETosis.
Antioxidant Compound Disease ModelsClinical StatusMechanism of ActionEffect on NETosisReference
Vitamin CNon-specificPreclinical
study		Enhances redox balance and scavenges ROS.Dose-dependent reduction in NET formation; complete prevention at pharmacological concentrations.[44]
Trolox, TempolNon-specificPreclinical
study		Scavenge ROS and inhibit enzymes responsible for ROS synthesis.Inhibit ROS-dependent NET release.[50]
Catalase Pan-inflammationPreclinical
study		Enhances redox balance and scavenges ROS.Inhibits NETosis via H2O2 scavenging.[5,51]
ProanthocyanidinLiver CancerPreclinical
study		Significantly reducing ROS levels in neutrophils.Blocks the oxidative stress pathways required for chromatin decondensation and NET release.[52]
N-Acetyl Cysteine (NAC)Non-specificPreclinical
study		Combined with GSH, it abolishes NET formation in LPS-stimulated neutrophils.Reduces NETs by scavenging ROS and inhibiting MPO activity.[44,45]
ResveratrolNon-specific
SARS-CoV-2 infection		Preclinical
Study
Preclinical
study		Inhibits myeloperoxidase release, particularly when stimulated with PMA and POVPC, and
reduces oxidative stress.		Suppresses DNA release from neutrophils.
Decreases the neutrophil-activated status and the release of free DNA, inhibiting NET formation.		[47,49]
Glutathione (GSH)Non-specificPreclinical
study		Improves intracellular antioxidant capacity and GSH/GSSG ratio.Strong suppression of NET formation in serum and intracellular levels.[44]
butylated hydroxytoluene (BHT)Non-specificPreclinical
study		Enhances redox balance and scavenges ROS.Reduces NET formation in vitro.[53]
MetforminDiabetesPreclinical and clinical
study		Inhibits PKC-NADPH oxidase pathway.Reduces NET components and blunts NETosis in vitro.[46]
Thiocyanate, Selenocyanate, NitroxidesChronic InflammationPreclinical
study		Modulate HOCl production by MPO.Prevent NETosis in PLB-985 neutrophils exposed to PMA and HOCl.[45]
MitoTEMPO Chronic obstructive pulmonary disease (COPD)Preclinical and clinical
study		Prevents NADPH oxidase activation.Reduces NETosis in specific contexts (e.g., COPD mouse model).[54]
Diphenyleneiodonium (DPI)ThrombosisPreclinical and clinical
study		Inhibition of NOX2.Identifies NOX2 inhibition as a potential new therapeutic target for antithrombotic treatment.[55]
Peroxiredoxin (Prdx)Inflammatory bowel disease (IBD)Preclinical
study		Upregulation in response to voluntary exercise.Reduces inflammation and inhibits NETosis in TNBS (induce experimental colitis).[56]
(+)-BorneolNon-specificPreclinical
study		Inhibits ROS generation and NADPH oxidase activity.Decreases ROS levels and inhibits NETosis triggered by PMA stimulation.[57]
Anthracyclines (e.g., Epirubicin, Daunorubicin)Non-specificPreclinical
study		Suppress both NADPH oxidase-dependent and -independent NETosis.Inhibit NETosis without suppressing ROS necessary for antimicrobial functions.[58]
Indolylmaleimide Derivative IM-93Non-specificPreclinical
study		Inhibits oxidative stress-induced necrotic cell death.Inhibits both ferroptosis and NETosis.[59]
Combination TherapiesNon-specificPreclinical
study		Enhances TAC and reduces ROS/RNS levels.Most effective approach; achieves strongest suppression of NET formation using Vit E + Vit C + GSH + NAC.[44]
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Zambrano, F.; Uribe, P.; Schulz, M.; Hermosilla, C.; Taubert, A.; Sánchez, R. Antioxidants as Modulators of NETosis: Mechanisms, Evidence, and Therapeutic Potential. Int. J. Mol. Sci. 2025, 26, 5272. https://doi.org/10.3390/ijms26115272

AMA Style

Zambrano F, Uribe P, Schulz M, Hermosilla C, Taubert A, Sánchez R. Antioxidants as Modulators of NETosis: Mechanisms, Evidence, and Therapeutic Potential. International Journal of Molecular Sciences. 2025; 26(11):5272. https://doi.org/10.3390/ijms26115272

Chicago/Turabian Style

Zambrano, Fabiola, Pamela Uribe, Mabel Schulz, Carlos Hermosilla, Anja Taubert, and Raúl Sánchez. 2025. "Antioxidants as Modulators of NETosis: Mechanisms, Evidence, and Therapeutic Potential" International Journal of Molecular Sciences 26, no. 11: 5272. https://doi.org/10.3390/ijms26115272

APA Style

Zambrano, F., Uribe, P., Schulz, M., Hermosilla, C., Taubert, A., & Sánchez, R. (2025). Antioxidants as Modulators of NETosis: Mechanisms, Evidence, and Therapeutic Potential. International Journal of Molecular Sciences, 26(11), 5272. https://doi.org/10.3390/ijms26115272

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