Simon Gissing, Eva-Maria Pferschy-Wenzig, Ramona Jeitler, Michael Russwurm, Astrid Schrammel, Bernd Mayer, Alexander Kollau
{"title":"Unsaturated fatty acids identified as reversible soluble guanylyl cyclase inhibitors.","authors":"Simon Gissing, Eva-Maria Pferschy-Wenzig, Ramona Jeitler, Michael Russwurm, Astrid Schrammel, Bernd Mayer, Alexander Kollau","doi":"10.1016/j.niox.2025.10.005","DOIUrl":"https://doi.org/10.1016/j.niox.2025.10.005","url":null,"abstract":"<p><p>As key enzyme in the NO/cGMP pathway, soluble guanylyl cyclase (sGC) has become an important therapeutic target in the treatment of cardiovascular diseases. In addition to activating compounds, inhibitors of sGC are necessary tools in research and may even be desirable as therapeutic agents in certain situations, like migraine. In a previous study we observed reversible inhibition of isolated sGC by aqueous extracts from tobacco cigarette smoke. In the current study, we found that extracts prepared from cured tobacco share these properties. The active compounds were isolated and identified as unsaturated fatty acids. Further characterization of the inhibitory effect indicated a potential interaction with the heme binding site. In addition, initial experiments with vascular endothelial cells suggest that the observed effect may be relevant to blood vessels function in vivo.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Versatile Vanadium(III)-Based Chemiluminescence Protocol for Nitric Oxide Metabolite Quantification and NO Release Kinetics.","authors":"Joseph A Bauer, Annette M Sysel, Michael J Dunphy","doi":"10.1016/j.niox.2025.10.006","DOIUrl":"https://doi.org/10.1016/j.niox.2025.10.006","url":null,"abstract":"<p><p>Nitric oxide (NO) is a central mediator of vascular, neurological, and immune functions, and its dysregulation is implicated in a broad spectrum of diseases. Despite its significance, direct measurement of NO in human samples is limited by its transient nature and rapid conversion to nitrate and nitrite. Accurate, rapid, and accessible quantification of these NO metabolites in clinical and research settings remains a key need. We present a vanadium(III)-based chemiluminescence protocol for the reliable detection of nitrate and nitrite in human biological fluids, including serum, urine, and cerebrospinal fluid. In addition, this method supports headspace gas analysis, enabling precise determination of nitric oxide release kinetics and half-life from NO-producing compounds. This approach offers a cost-effective and scalable solution suitable for routine analysis in both diagnostic and research laboratories.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Roles of nitric oxide in improving post-harvest horticultural product quality: Crosstalk with hydrogen sulfide.","authors":"Yali Qiao, Yayu Liu, Jihua Yu, Weibiao Liao","doi":"10.1016/j.niox.2025.10.004","DOIUrl":"https://doi.org/10.1016/j.niox.2025.10.004","url":null,"abstract":"<p><p>Postharvest quality maintenance is a key research focus in horticultural science. Nitric oxide (NO), a vital gaseous signaling molecule, significantly improves postharvest quality by inhibiting ethylene (ETH) synthesis, reducing respiration rate, enhancing antioxidant enzyme systems, maintaining cell wall integrity, and regulating secondary metabolism. Currently, the synergistic mechanisms between NO and hydrogen sulfide (H<sub>2</sub>S) have emerged as a research hotspot. The two molecules work in concert to delay postharvest senescence and enhance fruit resistance to low temperature and pathogens involving enzyme activity regulation and physiological synergy. This review provides a comprehensive analysis of the independent regulatory effects of NO and its crosstalk mechanisms with H<sub>2</sub>S, providing theoretical foundations for developing efficient and safe postharvest preservation technologies and highlighting their potential applications in green preservation.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuriy E Kolupaev, Tetiana O Yastreb, Alla Yemets, Yaroslav Blume
{"title":"NITRIC OXIDE FUNCTIONAL RELATIONSHIPS WITH NITROGEN-CONTAINING STRESS METABOLITES: ROLE IN PLANT ADAPTATION TO ADVERSE ABIOTIC FACTORS.","authors":"Yuriy E Kolupaev, Tetiana O Yastreb, Alla Yemets, Yaroslav Blume","doi":"10.1016/j.niox.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.niox.2025.10.003","url":null,"abstract":"<p><p>Polyamines, γ-aminobutyric acid (GABA), proline, and glycine betaine (GB) are important plant stress metabolites that are interconnected in common metabolic cycles. These compounds have a multifunctional protective effect on plant cells under stress conditions, acting as osmoregulators, antioxidants, chaperones, and intracellular pH stabilizers, among other roles. The key role of these compounds, however, lies in their involvement in the signaling network of plant cells. Stress metabolites, in particular, engage in a complex functional interaction with reactive oxygen species (ROS) and nitric oxide (NO). Nevertheless, information detailing the links between NO and major nitrogen-containing stress metabolites is fragmented. Consequently, a holistic understanding of these interactions, even at the theoretical model level, has yet to be presented in the literature. The review investigates the phenomenology and mechanisms of NO's involvement as a signaling mediator in the stress-protective function of polyamines and GABA in plants. It also analyses the effect of NO on the content of polyamines, GABA, proline, and GB under normal and stressful conditions. The latest data on the role of S-nitrosation processes of enzymes involved in the regulation of content of low-molecular nitrogen-containing compounds in plant adaptation, and on the effect of polyamines on S-nitrosation of the proteome are summarized. Particular attention is paid to the links between nitric oxide and other signaling mediators (primarily ROS and Ca<sup>2+</sup>) during its functional interaction with stress metabolites. Regulation of NO and stress metabolite levels is considered one of the promising tools for managing plant stress resistance.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diabetic nephropathy: Role of nitric oxide.","authors":"Sajad Jeddi, Khosrow Kashfi, Asghar Ghasemi","doi":"10.1016/j.niox.2025.10.001","DOIUrl":"10.1016/j.niox.2025.10.001","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is characterized by structural kidney alterations-including glomerular basement membrane thickening, mesangial expansion, tubulointerstitial fibrosis, and glomerular hypertrophy-alongside functional impairments such as reduced glomerular filtration rate (GFR) and albuminuria. DN progresses through five stages: pre-nephropathy, silent, incipient, overt nephropathy, and end-stage kidney disease (ESKD). Dysregulation of the nitric oxide synthase (NOS) pathway-including neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS)-has been increasingly implicated in DN pathogenesis. Evidence from preclinical models using NOS inhibitors and knockout mice, combined with human studies that identify NOS gene polymorphisms, supports this association. In early stages, hyperglycemia elevates GFR, driven by increased NO production from all three NOS isoforms. As the disease progresses, reduced eNOS-derived NO and persistent iNOS overexpression contribute to structural damage and a decline in GFR. NO donors have been shown to prevent early hyperfiltration and attenuate the subsequent decrease in GFR and renal injury characteristic of overt nephropathy. Thus, NO signaling plays a dual role in DN progression and represents a promising target for therapeutic intervention.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":"89-101"},"PeriodicalIF":3.2,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diabetic peripheral neuropathy: Role of nitric oxide.","authors":"Zahra Bahadoran, Asghar Ghasemi","doi":"10.1016/j.niox.2025.10.002","DOIUrl":"https://doi.org/10.1016/j.niox.2025.10.002","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is one of the most prevalent long-term complications in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and is characterized by structural (microangiopathy, axonal atrophy, impaired myelination, and disrupted Schwann cell-axon interactions) and functional (impaired axonal transport and sensory and motor disorders) changes in neurons. Nitric oxide (NO) contributes to the development and progression of DPN as it has a role in the perfusion and electrophysiological functions of neurons. NO is essential for sustaining nerve conduction velocity (NCV) through modulation of Na<sup>+</sup>/K<sup>+</sup>-ATPase activity. Isoform-specific alterations in NO synthase (NOS) expression and activity occur during the development of DPN. Neural NOS (nNOS) generally exhibits consistent downregulation, especially in T2DM models, whereas inducible NOS (iNOS) tends to be upregulated in the T1DM model. NO has been proposed as a potential therapeutic agent for DPN because of its potent vasodilatory effects. NO-donating derivatives (e.g., NCX1404, PRG150) have demonstrated both symptomatic and disease-modifying effects in DPN. In conclusion, NO plays a role in the pathophysiology of DPN and is a therapeutic target for managing neuropathy in diabetes.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"5-HT7 receptor antagonist SB269970 attenuates seizures by modulating NO/cGMP signaling pathway and neuroinflammation in a pentylenetetrazol-induced epilepsy model in rats","authors":"Handan Gunes, Ercan Ozdemir, Ahmet Sevki Taskiran","doi":"10.1016/j.niox.2025.09.006","DOIUrl":"10.1016/j.niox.2025.09.006","url":null,"abstract":"<div><div>Epilepsy is a disease affecting the quality of life, characterized by neuronal excessive discharges resulting from the disruption of the balance between excitatory and inhibitory systems in the brain, and its pathophysiology has not been fully elucidated. In this study, we investigated the effects of serotonin 7 (5-HT7) receptor antagonist SB 269970 on seizures in a pentylenetetrazol (PTZ)-induced epilepsy model. Seventy male Wistar Albino rats (weight 230–250 g) were used in the study and the rats were randomly assigned to control and drug groups. Predetermined doses of SB 269970 (3 mg/kg), 5-HT7 agonist AS 19 (5 mg/kg), 7-NI (nNOS inhibitor, 50 mg/kg), YC-1 (guanylate cyclase activator, 10 μg/kg) were administered to the rats. PTZ (35 mg/kg) was injected intraperitoneally to induce seizures. The Racine scale was used to evaluate seizure stages. After electrocorticography (ECoG) and video recordings, the rats were sacrificed and nitric oxide (NO), cGMP, nNOS and proinflammatory cytokines (TNF-α, IL-1β and IL-6) levels in hippocampal tissue were measured by biochemical methods. The study results showed that the seizure threshold increased and the number of seizures decreased in rats administered SB 269970. In addition, the levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and NO, cGMP and nNOS, which are increased with seizures in the hippocampal tissue, were significantly decreased by the administration of SB 269970. In contrast, the administration of 5-HT7 agonist AS-19 increased the number of seizures and caused an increase in the levels of hippocampal proinflammatory cytokines and NO, cGMP and nNOS. In conclusion, the findings of this study revealed that SB 269970 causes anticonvulsant activity by inhibiting the NO/cGMP pathway and proinflammatory cytokine (TNF-α, IL-1β and IL-6) levels in the hippocampal tissue. However, further molecular studies are needed for 5-HT7 antagonist drugs to be an option in the treatment of epilepsy.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 78-88"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nitric oxide tuning enhances cytotoxicity and reduces inflammation in prostate cancer nanotherapy.","authors":"Joana Claudio Pieretti, Giovana Marchini Armentano, Marcela Sorelli Carneiro-Ramos, Amedea Barozzi Seabra","doi":"10.1016/j.niox.2025.08.001","DOIUrl":"10.1016/j.niox.2025.08.001","url":null,"abstract":"<p><p>Modulating intracellular nitric oxide (NO) levels offers a promising strategy to enhance tumor cell sensitivity to nanoparticle-based therapies. In this study, we investigated the impact of intracellular NO modulation in prostate cancer cells (PC3) using S-nitrosoglutathione (GSNO, a NO donor) and L-nitro arginine methyl ester (l-NAME, a nitric oxide synthase (NOS) inhibitor), in combination with cisplatin-loaded zinc oxide nanoparticles (ZnO/CisPt NPs). These nanoparticles, previously shown to exert selective cytotoxicity against PC3 cells, had their therapeutic performance further enhanced by NO modulation, which led to reduced NOS expression and regulation of inflammatory cytokines. Interestingly, both the increase and the depletion of intracellular S-NO levels contributed to tumor cell sensitization to the nanoparticle-based treatment. These results indicate that altering NO balance, regardless of direction, plays a key role in how cells respond to therapy. Our results reinforce the relevance of NO signaling in augmenting the efficacy of nanomedicine approaches while minimizing tumor-associated inflammation, offering a safer and more targeted strategy for prostate cancer treatment with potential for broader applications in oncology.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":"124-131"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection and proteomic identification of in vivo S-nitrosylated proteins in Vibrio cholerae: A novel evidence","authors":"Shuddhasattwa Samaddar , Surupa Chakraborty , Rajib Sengupta , Sanjay Ghosh","doi":"10.1016/j.niox.2025.09.005","DOIUrl":"10.1016/j.niox.2025.09.005","url":null,"abstract":"<div><div>Conserved across the phylogeny, S-nitrosylation and S-denitrosylation of biological thiols is a reversible protein post-translational modification of cysteine thiol residues involving nitric oxide (NO) and NO<sup>•</sup>-derived metabolites. S-nitrosylation of proteins is observed to transduce signalling pathways with significant pathological and physiological relevance. Although endogenous S-nitrosylation is also an obligate non-classical cellular signalling pathway of NO<sup>•</sup> in single-celled organisms, but very little information is available in prokaryotes. Hitherto unknown, we present experimental evidence for the first time in vivo S-nitrosylation (without using any NO<sup>•</sup>/RNS donor) of proteins of the enteropathogenic, Gram-negative bacteria O1 El Tor strains of <em>Vibrio cholerae</em> N16961 and C6706. In the present study, PSNO was quantified by 2, 3-diaminonaphthalene (DAN) using a spectrofluorometer, which was further supported by confocal microscopy. Western blot and mass spectrometry-based proteomic analyses identified ten S-nitrosylated proteins <em>via</em> DMPO-nitrone adduct formation. <em>V. cholerae</em> contained high amounts of the in vivo pool of S-nitrosylated proteome in different respiratory conditions. Experimental evidence shows that physiological levels of glutathione (GSH) can efficiently S-denitrosylate <em>Vibrio cholerae</em> PSNO in a concentration-dependent manner, suggesting that the intracellular GSH tends to reset the redox state of these protein thiols. Our data suggests that <em>V. cholerae</em> possesses more amount of in vivo PSNO during semi-anaerobic respiration than aerobic respiration and irrespective of media and strain used; stationary phase cells are relatively more stable to GSH-catalyzed S-denitrosylation than their log-phase counterparts. Additionally, the in vivo PSNO accumulation was found to be elevated in the nitrate reductase deletion mutant <em>(</em>Δ<em>napA</em>), indicating the role of <em>napA</em> in the nitroso-oxidative stress response mechanism of <em>V. cholerae</em>. This could aid in its remarkable adaptability and survivability in the hostile conditions of the human intestine, thereby paving the way for cholera, a highly contagious diarrheal disease.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 63-77"},"PeriodicalIF":3.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brenda da Silva , Fernanda Tibolla Viero , Caren Tatiane de David Antoniazzi , Sabrina Qader Kudsi , Diulle Spat Peres , Ricardo Iuri Felix Morais , Leonardo Gomes Pereira , Gabriela Trevisan
{"title":"7-Nitroindazole, an nNOS inhibitor, reduces migraine-like nociception, demyelination, and anxiety-like behavior in a mouse model of relapsing-remitting multiple sclerosis","authors":"Brenda da Silva , Fernanda Tibolla Viero , Caren Tatiane de David Antoniazzi , Sabrina Qader Kudsi , Diulle Spat Peres , Ricardo Iuri Felix Morais , Leonardo Gomes Pereira , Gabriela Trevisan","doi":"10.1016/j.niox.2025.09.003","DOIUrl":"10.1016/j.niox.2025.09.003","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a complex neuroinflammatory disease often associated with migraine and anxiety, both of which impair quality of life. MS pathology involves intense inflammatory and oxidative processes, including increased nitric oxide (NO) production. However, the role of NO in MS-related migraine symptoms remains unclear. This study evaluated whether repeated administration of 7-nitroindazole (7-NI), a selective neuronal nitric oxide synthase (nNOS) inhibitor, could alleviate migraine-like nociception, anxiety-like behavior, and neuroinflammatory biomarkers in a relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mouse model. RR-EAE was induced in female C57BL/6 mice (20–30 g) using myelin oligodendrocyte glycoprotein (MOG35-55) and Quillaja saponin as an adjuvant. Mice received daily intragastric 7-NI (120 mg/kg) from day 20–35 post-induction. Disease progression, mechanical/spontaneous allodynia, and anxiety-like behavior were assessed. At the end of the protocol, oxidative and inflammatory biomarkers were analyzed. 7-NI treatment significantly reduced disease severity and nociception, exerted an anxiolytic effect, and improved myelin quality parameters. It inhibited the increase of oxidative and nitrosative markers (NOx, H<sub>2</sub>O<sub>2</sub>) in the brainstem, trigeminal ganglion, and plasma. Treatment also prevented plasma calcitonin gene-related peptide elevation and increased anti-inflammatory cytokines (IL-4, IL-10), suggesting positive modulation of neuroinflammation in RR-EAE. These findings highlight the therapeutic potential of 7-NI in MS; however, further studies are required to confirm its safety and efficacy in different populations and chronic disease contexts.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 51-62"},"PeriodicalIF":3.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}