ABSTRACT
INTRODUCTION: The urgent problem of modern medicine is the fight against acute respiratory viral infections (ARVI). To combat ARVI, drugs of wide antiviral potency are needed, as well as immunomodulating drugs. Such antiviral and immunomodulatory effects has sodium deoxyribonucleate (DNA-Na) and its complex with iron (DNA-Na-Fe) developed on the basis of double-stranded DNA of natural origin. AIM OF THE STUDY: To assess antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against viruses of different kingdoms and families. MATERIALS AND METHODS: Antiviral and virucidal activity of DNA-Na and DNA-Na-Fe was assessed in cell cultures infected with viruses. RESULTS AND DISCUSSION: DNA-Na and DNA-Na-Fe had antiviral activity against adenovirus at concentrations of 2501000 mcg/ml. Antiviral effect of both drugs was not detected in case of poliovirus. DNA-Na and DNA-Na-Fe had antiviral activity against coronavirus in all administration schemes. EC50 for DNA-Na ~ 2500 mcg/ml, for DNA-Na-Fe ~ 1000 mcg/ml. In cells treated with DNA-Na-Fe, secretion of following proinflammatory cytokines was detected: Interleukin (IL) 1, IL-2, IL-6, IL-18, interferon- (IFN-), IFN-, as well as anti-inflammatory cytokines: IL-4, IL-10, antagonist of IL-1 receptor. Evidently, DNA-Na and DNA-Na-Fe have antiviral effect, but mechanism of action does not seem to be associated with specific effect on viral replication. Presence of virucidal activity of drugs against representatives of Coronaviridae, Adenoviridae, Picornaviridae, Retroviridae, Herpesviridae in vitro test in range of 1.03.0 lg TCID50 was identified. CONCLUSION: Presence of simultaneous antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against adeno- and coronaviruses shows their prospects for prevention and treatment of ARVI.
Subject(s)
Coronavirus Infections , Coronavirus , Herpesviridae , Respiratory Tract Infections , Virus Diseases , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Iron/pharmacology , Iron/therapeutic use , Sodium/pharmacology , Sodium/therapeutic use , Virus Diseases/drug therapy , Adenoviridae , CytokinesABSTRACT
Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells. After axon transection, stretch receptors were isolated and incubated in saline in the presence or without specific inhibitors of various signaling proteins. Inhibition of MEK1/2, p38, Akt, GSK-3ß and mTOR increased axotomy-induced apoptosis of remote glial cells, whereas inhibition of ERK1/2 and GSK-3ß enhanced necrosis. This suggests the involvement of these signaling proteins in protective, antiapoptotic and antinecrotic processes in the remote satellite glia surrounding the axotomized mechanoreceptor neuron.
Subject(s)
Apoptosis , Axons/metabolism , MAP Kinase Signaling System , Mechanoreceptors/metabolism , Neuroglia/metabolism , AMP-Activated Protein Kinase Kinases , Animals , Astacoidea , Cells, Cultured , Glycogen Synthase Kinase 3 beta/metabolism , MAP Kinase Kinase 1/metabolism , MAP Kinase Kinase 2/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Necrosis , Protein Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
BACKGROUND: Radachlorin, a chlorine-derived photosensitizer, is used currently in photodynamic therapy (PDT) of skin cancer. In this work we studied Radachlorin-PDT effect on peripheral nerve and glial cells that are damaged along with tumor tissue. METHODS: We used simple model objects - a crayfish stretch receptor that consists of a single sensory neuron surrounded by glial cells and crayfish nerve cord consisting of nerve fibers and ganglia. Radachlorin absorption and emission spectra were registered using spectrophotometer and spectrofluorimeter. Radachlorin accumulation and intracellular localization were studied using the fluorescence microscope. Necrotic and apoptotic cells were visualized using propidium iodide and Hoechst 33342. Neuronal activity was registered using standard electrophysiological methods. RESULTS: Radachlorin absorption spectrum in the physiological van Harreveld saline (pH 7.3) contained maximums at 420 and 654nm. Its fluorescence band 620-700nm had a maximum at 664nm. In the crayfish stretch receptor Radachlorin localized predominantly to the glial envelope and penetrated slightly into the neuron body and axon. Radachlorin rapidly accumulated in the crayfish nerve cord tissue within 30min. Its elimination in the dye-free solution occurred slower: 11% loss for 2h. Radachlorin-PDT inactivated the neuron and induced necrosis of neurons and glial cells and glial apoptosis at concentrations as low as 10(-10)-10(-9)M. CONCLUSIONS: Radachlorin rapidly accumulates in the nervous tissue, mainly in glial cells, and demonstrates very high photodynamic efficacy that characterize it as a promising photosensitizer.
