INO-4885 / Rocket Pharma - LARVOL DELTA

Updated Reaction Pathway for Dichloramine Decomposition: Formation of Reactive Nitrogen Species and N-Nitrosodimethylamine. (PubMed, Environ Sci Technol) - "NHCl, NO, and DO profiles indicated that reactive nitrogen species (RNS) formed during NHCl decomposition, including nitroxyl/nitroxyl anion (HNO/NO) and peroxynitrous acid/peroxynitrite anion (ONOOH/ONOO)...A kinetic model accurately simulated NHCl, NHCl, NDMA, and DO concentrations and included (1) the unified model of chloramine chemistry revised with HNO as a direct product of NHCl hydrolysis; (2) HNO/NO then reacting with (i) HNO to form NO, (ii) DO to form ONOOH/ONOO, or (iii) NHCl or NHCl to form nitrogen gas; and (3) NDMA formation via ONOOH/ONOO or their decomposition products reacting with (i) dimethylamine (DMA) and/or (ii) chlorinated unsymmetrical dimethylhydrazine (UDMH-Cl), the product of NHCl and DMA. Overall, updated NHCl decomposition pathways are proposed, yielding (1) RNS via and (2) NDMA via ."

Journal

Protective effects of hydrogen against irradiation. (PubMed, Curr Pharm Des) - "The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances of in the treatment of H2 as a new class of radioprotective agents."

Journal • Fibrosis • Infectious Disease • Pneumonia • Respiratory Diseases

Cadmium exposure induces inflammation through the canonical NF-κΒ pathway in monocytes/macrophages of Channa punctatus Bloch. (PubMed, Fish Shellfish Immunol) - "Also Cd triggered ROS generation, reduced cellular NO levels by forming peroxynitrite along with the upregulated expression of inflammatory marker iNOS (inducible nitric oxide synthase) in monocyte/macrophages, both at mRNA and protein levels, indicating inflammation...TNF-α, IL-1β, IL-6, IL-12 along with a central inflammatory mediator NF-κΒ and downregulation of the anti-inflammatory cytokine IL-10, both at mRNA and protein level. It can be concluded that, a sub-lethal exposure of Cd in C. punctatus for 7 days caused significant alterations in the hematological, histological and ultrastructural profile in monocyte/macrophages; impaired innate immune parameters, triggers ROS generation and inflammation as validated from the upregulated expression of NF-κΒ, iNOS, TNF-α, IL-1β, IL-6, IL-12 and IL-10 down regulation."

Journal • Immune Modulation • Immunology • Inflammation • IL10 • IL12A • IL1B • IL6 • MPO • TNFA

Ferroptosis and Acetaminophen Hepatotoxicity - Are We Going Down Another Rabbit Hole? (PubMed, Gene Expr) - "This results in a mitochondrial oxidant stress, which requires amplification through a mitogen activated protein kinase cascade leading ultimately to enough reactive oxygen and peroxynitrite formation to trigger the mitochondrial membrane permeability transition and cell death... Under pathophysiologically relevant conditions, there is no evidence for quantitatively enough LPO to cause cell death and thus APAP hepatotoxicity is not caused by ferroptosis. However, the role of mitochondria localized minor LPO remains to be further investigated."

Journal • Hepatology • Liver Failure

Catalytic Antioxidants in the Kidney. (PubMed, Antioxidants (Basel)) - "Catalytic antioxidants are defined as small molecular mimics of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and some of them function as potent detoxifiers of lipid peroxides and peroxynitrite. Several catalytic antioxidants have been demonstrated to be effective in a variety of in vitro and in vivo disease models that are associated with oxidative stress, including kidney diseases. This review summarizes the evidence for the role of antioxidant enzymes in kidney diseases, the classifications of catalytic antioxidants, and their current applications to kidney diseases."

Journal • Review • Acute Kidney Injury • Chronic Kidney Disease • Diabetic Nephropathy • Nephrology • Renal Disease • CAT

A novel borate fluorescent probe for rapid selective intracellular peroxynitrite imaging. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "The probe shows high fluorescence response to ONOO in a wide pH range (7.0-11.5). Moreover, the probe exhibit good permeability, and the content of ONOO in cancer cells and normal cells was successfully monitored."

Journal • Oncology

Indication of Dynamic Peroxynitrite Fluctuations in the Rat Epilepsy Model with a Near-Infrared Two-Photon Fluorescent Probe. (PubMed, Anal Chem) - "With the assistance of TP fluorescence imaging in the epileptic brain tissue, we hypothesize that the abnormal levels of ONOO may serve as a potential indicator for the diagnosis of epilepsy. The TP fluorescence imaging based on DCM-ONOO provides a great potential approach for understanding the epilepsy pathology and diagnosis."

Journal • CNS Disorders • Epilepsy • Immunology

ICG/l-Arginine Encapsulated PLGA Nanoparticle-Thermosensitive Hydrogel Hybrid Delivery System for Cascade Cancer Photodynamic-NO Therapy with Promoted Collagen Depletion in Tumor Tissues. (PubMed, Mol Pharm) - "Moreover, ROS could further oxidize NO to generate peroxynitrite anions (ONOO)...PLGA@ICG@l-Arg/Gel significantly increased the antitumor efficacy against highly malignant 4T1 tumors in mice. Taken together, PLGA@ICG@l-Arg/Gel is a multifunctional platform that provides a novel strategy for cancer treatment with cascade amplification of the ROS oxidation effect, which holds great potential in clinical translation."

Journal • Hepatology • Oncology

"OK @Dereklowe time to dust off amyloid again! We all know it's those pesky peroxynitrites right?" (@MrGump13)

Exposure to diesel exhaust particles results in altered lung microbial profiles, associated with increased reactive oxygen species/reactive nitrogen species and inflammation, in C57Bl/6 wildtype mice on a high-fat diet. (PubMed, Part Fibre Toxicol) - "Our findings suggest that exposure to DEP causes persistent and sustained inflammation and bacterial alterations in a ROS-RNS mediated fashion, which is exacerbated by concurrent consumption of an HF diet."

IO biomarker • Journal • Chronic Obstructive Pulmonary Disease • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Lung Cancer • Pneumonia • Respiratory Diseases • Solid Tumor • NFKB1 • TLR4 • TNFA

Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry. (PubMed, Mol Neurobiol) - "Given its key role in governing the cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder and schizophrenia, which are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide and peroxynitrite...Coenzyme Q, which acts as a superoxide scavenger in neuroglial mitochondria, instigates mitohormesis, ameliorates lipid peroxidation in the inner mitochondrial membrane, activates uncoupling proteins, promotes mitochondrial biogenesis and has positive effects on the plasma membrane redox system. Melatonin, which scavenges mitochondrial free radicals, inhibits mitochondrial nitric oxide synthase, restores mitochondrial calcium homeostasis, deacetylates and activates mitochondrial SIRT3, ameliorates increased permeability of the blood-brain barrier and intestine and counters..."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Immunology • Inflammation • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Dimethyl Fumarate Attenuates Lung Inflammation and Oxidative Stress Induced by Chronic Exposure to Diesel Exhaust Particles in Mice. (PubMed, Int J Mol Sci) - "Intracellular total reactive oxygen species (ROS), peroxynitrite (OONO), and nitric oxide (NO) levels were significantly lower in the DEP + DMF than in the DEP group...In summary, DMF treatment effectively reduced lung injury, inflammation, and oxidative and nitrosative stress induced by chronic DEP exposure. Consequently, it may lead to new therapies to diminish lung injury caused by air pollutants."

Journal • Immunology • Inflammation • Pneumonia • Respiratory Diseases • CAT • GPX1 • KEAP1 • NFKB1

On the Liquid Chemistry of the Reactive Nitrogen Species Peroxynitrite and Nitrogen Dioxide Generated by Physical Plasmas. (PubMed, Biomolecules) - "A pilot study, identifying RNS driven post-translational modifications of proteins in healing human wounds after the treatment with cold plasma (kINPen), demonstrated the presence of in vitro determined chemical pathways. The plasma-driven nitration and nitrosylation of tyrosine allows the conclusion that covalent modification of biomolecules by RNS contributes to the clinically observed impact of cold plasmas."

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QUERCETIN LIMITS THE PROGRESSION OF OXIDATIVE AND NITROSATIVE STRESS IN THE RATS' TISSUES AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY. (PubMed, Wiad Lek) - " on the 7th day after modeling moderate TBI in rats the signs of oxidative-nitrosative stress are found not only in locus morbi (in the tissue of the cerebral hemisphere), but also in distant organs (periodontal tissues). Applying of water-soluble form of quercetin significantly reduces signs of oxidative-nitrosative stress in the tissue of the cerebral hemisphere of rats, as well as in periodontal tissues on the 7th day after moderate TBI modeling."

Journal • Anesthesia • CNS Disorders • Vascular Neurology

Alleviation of the chronic stress response attributed to the antioxidant and anti-inflammatory effects of electrolyzed hydrogen water. (PubMed, Biochem Biophys Res Commun) - "Since molecular hydrogen is known to preferentially remove cytotoxic hydroxyl radicals and peroxynitrites, and to prevent cell and tissue damage, we here examined whether electrolyzed hydrogen water (EHW) enriched with molecular hydrogen and reactive hydrogen storing platinum nanoparticles dissolved from an electrode could alleviate oxidative stress and inflammation induced by continuous stress challenges...Drinking EHW during 5-day continuous stress loading significantly alleviated all of these changes. The results suggest that EHW could suppress stress-response-associated oxidative stress and IL-1β level elevation in vivo, and that drinking of EHW is effective for controlling stress responses via its antioxidant potential."

Journal • Immunology • Inflammation • IL1B

NO Scavenging through Reductive Nitrosylation of Ferric Mycobacterium tuberculosis and Homo sapiens Nitrobindins. (PubMed, Int J Mol Sci) - "Ferric nitrobindins (Nbs) selectively bind NO and catalyze the conversion of peroxynitrite to nitrate...From the dependence of k on [OH], the values of the second-order rate constant k for the reductive nitrosylation of Mt-Nb(III)-NO and Hs-Nb(III)-NO were obtained (4.9 (±0.5) × 10 M s and 6.9 (±0.8) × 10 M s, respectively). This process leads to the inactivation of two NO molecules: one being converted to HNO and another being tightly bound to the ferrous heme-Fe(II) atom."

Journal • Infectious Disease • Respiratory Diseases • Tuberculosis

Antioxidant action of vitamin E in vivo as assessed from its reaction products with multiple biological oxidants. (PubMed, Free Radic Res) - "α-TQ is produced by multiple oxidants including oxygen radicals, peroxynitrite, hypochlorite, singlet oxygen, and ozone, while 5-NgT is produced by nitrogen dioxide radical derived from peroxynitrite and the reaction of nitrite and hypochlorite...These data indicate that vitamin E acts as an important physiological antioxidant and that α-TQ and 5-NgT represent biomarker for oxidative stress and nitrative stress respectively. (232 words)."

Journal • Preclinical • CNS Disorders

Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis. (PubMed, Clin Chim Acta) - "Our findings exhibit the functional role of iNOS-Rac2 interaction in ROS/RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death."

Journal • Infectious Disease • Lung Cancer • Oncology • Septic Shock • Solid Tumor

Mechanisms Underlying the Biological Effects of Molecular Hydrogen. (PubMed, Curr Pharm Des) - "Among the remarkable characteristics of H2 is its ability to counteract harmful effects of hydroxyl radical and peroxynitrite without affecting activity of functionally important ROS, such as hydrogen peroxide and nitric oxide...However, the exact targets and mechanism(s) by which H2 exerts these effects are unknown. Here we analyzed both positive and negative effects of the endogenous H2 , identified the redox-sensitive components of the pathways affected by molecular hydrogen, and also discussed a potential role of molecular hydrogen in regulating cellular redox."

Journal • Immunology • Inflammation

The Gut Microbiota, Kynurenine Pathway, and Immune System Interaction in the Development of Brain Cancer. (PubMed, Front Cell Dev Biol) - "With respect of brain cancer, gut microbiota could modify the levels of antioxidants, amyloid protein and lipopolysaccharides, arginase 1, arginine, cytochrome C, granulocyte-macrophage colony-stimulating factor signaling (GM-CSF), IL-4, IL-6, IL-13, IL-17A, interferon gamma (IFN-γ), reactive oxygen species (ROS), reactive nitrogen species (e.g., nitric oxide and peroxynitrite), short-chain fatty acids (SCFAs), tryptophan, and tumor necrosis factor-β (TGF-β)...This review scrutinizes the oncogenic and oncolytic effects of gut microbiota by classifying the modification mechanisms into (i) amino acid deprivation (arginine and tryptophan); (ii) kynurenine pathway; (iii) microglia dysbiosis; and (iv) myeloid-derived suppressor cells (MDSCs). By delineating the complexity of the gut-microbiota-brain-cancer axis, this review aims to help the research on the development of novel therapeutic strategies that may aid the efficient eradication of brain cancers."

Journal • Review • CNS Disorders • Glioblastoma • Immunology • Inflammation • Solid Tumor • CSF2 • IFNG • IL13 • IL17A • IL4 • IL6 • TNFA

Ormosanine improves neuronal functions in spinal cord-injured rats by blocking peroxynitrite/calpain activity. (PubMed, Transl Neurosci) - "Moreover, ormosanine treatment reduced the percentage of viable neurons in the spinal tissue of SCI rats. In conclusion, the results of this study showed that ormosanine treatment had a protective effect against neuronal injury in spinal cord-injured rats by regulating the peroxynitrite/calpain activity."

Journal • CNS Disorders • Complement-mediated Rare Disorders • Immunology • Inflammation • Orthopedics • PCR

Sequential Application of High-Voltage Electric Field Cold Plasma Treatment and Acid Blanching Improves the Quality of Fresh Carrot Juice (Daucus carota L.). (PubMed, J Agric Food Chem) - "AB-HVCP resulted in antimicrobial synergism, which is an outcome of acidified NO, HO, O, and peroxynitrites (ONOO) or its precursor OH/NO, along with other species. In addition, plasma treatment also promotes the accumulation of coloring compounds, chlorogenic acid, and sugar contents by surface erosion of the epidermal layer, cis isomerization, rupturing of phenol-sugar and phenolic-cell matrix bonds, and depolymerized long-chain polysaccharides by cleavage of the glycoside bond. Therefore, AB-HVCP is a potential emerging hurdle strategy for fresh produce."

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P-MAPA, a Fungi-Derived Immunomodulatory Compound, Induces a Proinflammatory Response in a Human Whole Blood Model. (PubMed, Mediators Inflamm) - "P-MAPA also induced the production of TNF-α, IL-8, and IL-12 and oxidative burst, measured by peroxynitrite levels, in human leukocytes...Altogether, our results show that P-MAPA induced proinflammatory response in human leukocytes, which is partially mediated by complement activation. Our data contribute to elucidate the complement-dependent and complement-independent mechanisms of P-MAPA, which ultimately result in immune cell activation and in its immunomodulatory properties in infection and cancer animal models."

IO Biomarker • Journal • Immune Modulation • Inflammation • Oncology • CD14 • CXCL8 • IL12A • ITGAM • TLR4

Novel near-infrared fluorescence probe with large Stokes shift for monitoring CCl-induced toxic hepatitis. (PubMed, Talanta) - "More and more studies have shown that peroxynitrite (ONOO) is related with the development of toxic hepatitis...More importantly, by visualizing ONOO, the probe was used to monitor the diagnosis of CCl-induced toxic hepatitis in mice and evaluate the therapeutic efficacy of hepatoprotective medicines (NAC, SM, DDB). The results show that the probe will provide a powerful tool for the diagnosis and treatment of toxic hepatitis."

Journal • Hepatology

Nutraceutical Induction and Mimicry of Heme Oxygenase Activity as a Strategy for Controlling Excitotoxicity in Brain Trauma and Ischemic Stroke: Focus on Oxidative Stress. (PubMed, Expert Rev Neurother) - "Expert opinion: Activation of both NADPH oxidase and neuronal nitric oxide synthase in the microenvironment of activated NMDA receptors drives production of superoxide and highly toxic peroxynitrite...Heme oxygenase-1 (HO-1) induction offers protection via inhibition of NADPH oxidase and promotion of cGMP generation. Phase 2-inductive nutraceuticals can induce HO-1, and other nutraceuticals can mimic the effects of its products biliverdin and carbon monoxide."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Metabolic Disorders • Mood Disorders • Vascular Neurology • HMOX1