Farmacocinética y farmacodinamia del dióxido de cloro

Chlorine dioxide (ClO2) is widely used as a drinking water disinfectant in many countries. Due to its antibiotic and antiviral capacity, it has aroused interest as a potential therapeutic agent with respect to the COVID-19 disease, AIDS and Influenza. As a result of this debate in scientific and governmental settings, it was deemed highly timely to provide an up-to-date assessment of the pharmacokinetics and pharmacodynamics of ClO2. The main findings indicate that, due to its high chemical reactivity, ClO2 is rapidly reduced in oral and gastric secretions, producing chlorite (ClO2⁻), which becomes the active agent responsible for its systemic actions. ClO2 also showed potential to act as an oxidant or antioxidant depending on the concentration. Of particular therapeutic interest are the findings that, at low concentrations, ClO2⁻ can protect erythrocytes from oxidative stress while inhibiting excessive production of hypochlorous acid (HClO) mediated by myeloperoxidase (MPO), thus reversing the inflammatory responses and macrophage activation. Finally, taurine-chloramine represents the most relevant functional product formed under the influence of ClO2⁻, said molecule activates the erythroid nuclear factor 2 (Nrf2), (this transcription factor regulates the inducible expression of numerous genes for detoxifying and antioxidant enzymes) , increases the expression of heme-oxygenase (HO-1), protects cells from death caused by hydrogen peroxide (H2O2), improves the expression and activities of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase, and contributes to the resolution of the inflammatory process.

Farmacocinética y farmacodinamia del dióxido de cloro

Chlorine dioxide (ClO2) is widely used as a drinking water disinfectant in many countries. Due to its antibiotic and antiviral capacity, it has aroused interest as a potential therapeutic agent with respect to the COVID-19 disease, AIDS and Influenza. As a result of this debate in scientific and governmental settings, it was deemed highly timely to provide an up-to-date assessment of the pharmacokinetics and pharmacodynamics of ClO2. The main findings indicate that, due to its high chemical reactivity, ClO2 is rapidly reduced in oral and gastric secretions, producing chlorite (ClO2⁻), which becomes the active agent responsible for its systemic actions. ClO2 also showed potential to act as an oxidant or antioxidant depending on the concentration. Of particular therapeutic interest are the findings that, at low concentrations, ClO2⁻ can protect erythrocytes from oxidative stress while inhibiting excessive production of hypochlorous acid (HClO) mediated by myeloperoxidase (MPO), thus reversing the inflammatory responses and macrophage activation. Finally, taurine-chloramine represents the most relevant functional product formed under the influence of ClO2⁻, said molecule activates the erythroid nuclear factor 2 (Nrf2), (this transcription factor regulates the inducible expression of numerous genes for detoxifying and antioxidant enzymes) , increases the expression of heme-oxygenase (HO-1), protects cells from death caused by hydrogen peroxide (H2O2), improves the expression and activities of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase, and contributes to the resolution of the inflammatory process.

Topically Applied Taurine Chloramine Protects against UVB-Induced Oxidative Stress and Inflammation in Mouse Skin

Excessive exposure to solar light, especially its UV component, is a principal cause of photoaging, dermatitis, and photocarcinogenesis. In searching for candidate substances that can effectively protect the skin from photodamage, the present study was conducted with taurine chloramine (TauCl), formed from taurine in phagocytes recruited to inflamed tissue. Irradiation with ultraviolet B (UVB) of 180 mJ/cm2 intensity caused oxidative damage and apoptotic cell death in the murine epidermis. These events were blunted by topically applied TauCl, as evidenced by the lower level of 4-hydroxynonenal-modified protein, reduced proportions of TUNEL-positive epidermal cells, and suppression of caspase-3 cleavage. In addition, the expression of two prototypic inflammatory enzymes, cyclooxygenase-2 and inducible nitric oxide synthase, and transcription of some pro-inflammatory cytokines (Tnf, Il6, Il1b, Il10) were significantly lower in TauCl-treated mice than vehicle-treated control mice. The anti-inflammatory effect of TauCl was associated with inhibition of STAT3 activation and induction of antioxidant enzymes, such as heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1, through activation of nuclear factor erythroid 2-related factor 2.

Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.

Taurine Protects against Postischemic Brain Injury via the Antioxidant Activity of Taurine Chloramine

Taurine is ubiquitously distributed in mammalian tissues and is highly concentrated in the heart, brain, and leukocytes. Taurine exerts neuroprotective effects in various central nervous system diseases and can suppress infarct formation in stroke. Taurine reacts with myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) to produce taurine chloramine (Tau-Cl). We investigated the neuroprotective effects of taurine using a rat middle cerebral artery occlusion (MCAO) model and BV2 microglial cells. Although intranasal administration of taurine (0.5 mg/kg) had no protective effects, the same dose of Tau-Cl significantly reduced infarct volume and ameliorated neurological deficits and promoted motor function, indicating a robust neuroprotective effect of Tau-Cl. There was neutrophil infiltration in the post-MCAO brains, and the MPO produced by infiltrating neutrophils might be involved in the taurine to Tau-Cl conversion. Tau-Cl significantly increased the levels of antioxidant enzymes glutamate–cysteine ligase, heme oxygenase-1, NADPH:quinone oxidoreductase 1, and peroxiredoxin-1 in BV2 cells, whereas taurine slightly increased some of them. Antioxidant enzyme levels were increased in the post-MCAO brains, and Tau-Cl further increased the level of MCAO-induced antioxidant enzymes. These results suggest that the neutrophils infiltrate the area of ischemic injury area, where taurine is converted to Tau-Cl, thus protecting from brain injury by scavenging toxic HOCl and increasing antioxidant enzyme expression.