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Adv Exp Med Biol ; 1370: 23-29, 2022.
Article in English | MEDLINE | ID: covidwho-1958872


The novel coronavirus disease (COVID-19), which is prevalent in the world, develops severe pneumonia, of which 30% have fatal acute respiratory distress and acute lung injury. At present, there is no established treatment method for ARDS, and it is desired to develop a therapeutic drug as soon as possible. While TauCl has been reported to have anti-inflammatory effects on culture cells, little information is available concerning in vivo experiments. In the present study, we evaluated the anti-inflammatory effect of taurine chloramine (TauCl), a taurine derivative, against LPS-induced pneumonia in mouse. The mice were pretreated with TauCl intraperitoneally before intratracheal administration of LPS. Additionally, we evaluated the effect of taurine treatment by maintaining the mice on drinking water containing 0.5% taurine. Two days after LPS injection, body weight was decreased by 9.5 %, while lung weight was increased due to the infiltration of inflammatory cells; TauCl attenuated the gain in lung weight. LPS-induced acute pneumonia caused an increase in cytokine/chemokine mRNA expression, including that of IL-1ß, -6, -17, TNF-α, and MCP-1. However, TauCl treatment attenuated IL-6 expression, but not that of the others although the induction of plasma IL-6 tended to be reduced by TauCl treatment. Importantly, a similar effect against LPS-induced acute lung inflammation was confirmed by taurine pretreatment. These findings suggest that TauCl treatment partially prevents IL-6 production induced by acute pneumonia in vivo.

COVID-19 , Lipopolysaccharides , Animals , Anti-Inflammatory Agents , Cells, Cultured , Interleukin-6 , Lipopolysaccharides/toxicity , Mice , Taurine/analogs & derivatives , Taurine/pharmacology , Taurine/therapeutic use
Emerg Microbes Infect ; 11(1): 1293-1307, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1788441


N-chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV). Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry. NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 -2 log10 reduction within 1-10 min). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log10 (H3N2) to 5 log10 (H1N1pdm), RSV by 4 log10 within a few min. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus haemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action. Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.

COVID-19 , Respiratory Tract Infections , COVID-19/drug therapy , Humans , Influenza A Virus, H3N2 Subtype , Respiratory Syncytial Viruses , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Taurine/analogs & derivatives
Sci Rep ; 11(1): 5402, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1123146


Most multiple sclerosis (MS) patients given currently available disease-modifying drugs (DMDs) experience progressive disability. Accordingly, there is a need for new treatments that can limit the generation of new waves T cell autoreactivity that drive disease progression. Notably, immune cells express GABAA-receptors (GABAA-Rs) whose activation has anti-inflammatory effects such that GABA administration can ameliorate disease in models of type 1 diabetes, rheumatoid arthritis, and COVID-19. Here, we show that oral GABA, which cannot cross the blood-brain barrier (BBB), does not affect the course of murine experimental autoimmune encephalomyelitis (EAE). In contrast, oral administration of the BBB-permeable GABAA-R-specific agonist homotaurine ameliorates monophasic EAE, as well as advanced-stage relapsing-remitting EAE (RR-EAE). Homotaurine treatment beginning after the first peak of paralysis reduced the spreading of Th17 and Th1 responses from the priming immunogen to a new myelin T cell epitope within the CNS. Antigen-presenting cells (APC) isolated from homotaurine-treated mice displayed an attenuated ability to promote autoantigen-specific T cell proliferation. The ability of homotaurine treatment to limit epitope spreading within the CNS, along with its safety record, makes it an excellent candidate to help treat MS and other inflammatory disorders of the CNS.

Central Nervous System/pathology , Multiple Sclerosis/immunology , T-Lymphocytes/immunology , Taurine/analogs & derivatives , Animals , Antigen Presentation/drug effects , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , Cell Proliferation/drug effects , Central Nervous System/drug effects , Central Nervous System/immunology , Disease Models, Animal , Disease Progression , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Mice, Inbred C57BL , Multiple Sclerosis/pathology , Myelin Proteolipid Protein/immunology , Peptide Fragments/immunology , Recurrence , Spleen/pathology , T-Lymphocytes/drug effects , Taurine/pharmacology , gamma-Aminobutyric Acid/pharmacology