Combined efficacy of oseltamivir, isoprinosine and ellagic acid in influenza A(H3N2)-infected mice.
Identifieur interne : 000A14 ( Main/Exploration ); précédent : 000A13; suivant : 000A15Combined efficacy of oseltamivir, isoprinosine and ellagic acid in influenza A(H3N2)-infected mice.
Auteurs : Elitsa L. Pavlova [Bulgarie] ; Lora S. Simeonova [Bulgarie] ; Galina A. Gegova [Bulgarie]Source :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [ 1950-6007 ] ; 2018.
Descripteurs français
- KwdFr :
- Acide ellagique (pharmacologie), Animaux, Antioxydants (pharmacologie), Antiviraux (pharmacologie), Association de médicaments (), Cellules rénales canines Madin-Darby, Chiens, Infections à Orthomyxoviridae (métabolisme), Infections à Orthomyxoviridae (traitement médicamenteux), Inosine pranobex (pharmacologie), Lignée cellulaire, Mâle, Oséltamivir (pharmacologie), Oxydoréduction (), Poumon (métabolisme), Poumon (virologie), Souris, Souris de lignée ICR, Sous-type H3N2 du virus de la grippe A (), Stress oxydatif (), Substances réactives à l'acide thiobarbiturique (métabolisme), Superoxide dismutase (métabolisme).
- MESH :
- métabolisme : Infections à Orthomyxoviridae, Poumon, Substances réactives à l'acide thiobarbiturique, Superoxide dismutase.
- pharmacologie : Acide ellagique, Antioxydants, Antiviraux, Inosine pranobex, Oséltamivir.
- traitement médicamenteux : Infections à Orthomyxoviridae.
- virologie : Poumon.
- Animaux, Association de médicaments, Cellules rénales canines Madin-Darby, Chiens, Lignée cellulaire, Mâle, Oxydoréduction, Souris, Souris de lignée ICR, Sous-type H3N2 du virus de la grippe A, Stress oxydatif.
English descriptors
- KwdEn :
- Animals, Antioxidants (pharmacology), Antiviral Agents (pharmacology), Cell Line, Dogs, Drug Therapy, Combination (methods), Ellagic Acid (pharmacology), Influenza A Virus, H3N2 Subtype (drug effects), Inosine Pranobex (pharmacology), Lung (metabolism), Lung (virology), Madin Darby Canine Kidney Cells, Male, Mice, Mice, Inbred ICR, Orthomyxoviridae Infections (drug therapy), Orthomyxoviridae Infections (metabolism), Oseltamivir (pharmacology), Oxidation-Reduction (drug effects), Oxidative Stress (drug effects), Superoxide Dismutase (metabolism), Thiobarbituric Acid Reactive Substances (metabolism).
- MESH :
- chemical , metabolism : Superoxide Dismutase, Thiobarbituric Acid Reactive Substances.
- chemical , pharmacology : Antioxidants, Antiviral Agents, Ellagic Acid, Inosine Pranobex, Oseltamivir.
- drug effects : Influenza A Virus, H3N2 Subtype, Oxidation-Reduction, Oxidative Stress.
- drug therapy : Orthomyxoviridae Infections.
- metabolism : Lung, Orthomyxoviridae Infections.
- methods : Drug Therapy, Combination.
- virology : Lung.
- Animals, Cell Line, Dogs, Madin Darby Canine Kidney Cells, Male, Mice, Mice, Inbred ICR.
Abstract
Influenza pathogenesis comprises a complex cascade of impaired cellular processes resulting from the viral replication and exaggerated immune response accompanied by reactive oxygen species (ROS) burst and oxidative stress, destructing membranous structures and tissues. By classical virological and biochemical methods we compared and evaluated the therapeutic effects of 2.5mg/kg/day of the antiviral drug - oseltamivir (OS), 500mg/kg/day of the immune modulator - isoprinosine (IP) and 500mg/kg/day of the antioxidant agent ellagic acid (EA) with a focus on their combined activities in influenza H3N2 virus-infected mice. The survival, lung pathology and titers, as well as the oxidative stress biomarker thiobarbituric acid reactive substances (TBARS) in the lungs, liver and blood plasma, correlated to the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione reductase (GR) were assessed. We found that the viral inhibitor applied together with the immune modulator and the antioxidant exhibited strong therapeutic effects on the survival of the influenza-challenged mice. That effect was mostly pronounced for the triple combination - protection index (PI) of 75.2%, mean survival time (MST) extended by 5.8 days compared to the PBS control and significant reduction of the lung titers by 1.38 Δlg; 2.3 scores lower lung pathology and 8 times reduction of the accumulated TBARS in the lungs and liver on the 5-th day p.i. The enzymatic assays revealed that this combination demonstrated very good protection against the damaging superoxide radicals (83% efficiency of SOD, in comparison to healthy controls 100%). The double combinations of OS with IP and EA also showed protective effects according to the virological analysis - PI of 53.1% and 54.5%. Ten times higher GR activity was observed when the combination EA+OS and monotherapy of EA were applied (96% in comparison to healthy controls 100%). The best antioxidant effect in blood plasma was observed in the EA+IP group - 4 times reduction in the TBARS-content compared to infected controls but it did not have any efficacy on the survival and lung injury.
DOI: 10.1016/j.biopha.2017.12.014
PubMed: 29241072
Affiliations:
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Le document en format XML
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<term>Antioxidants (pharmacology)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cell Line</term>
<term>Dogs</term>
<term>Drug Therapy, Combination (methods)</term>
<term>Ellagic Acid (pharmacology)</term>
<term>Influenza A Virus, H3N2 Subtype (drug effects)</term>
<term>Inosine Pranobex (pharmacology)</term>
<term>Lung (metabolism)</term>
<term>Lung (virology)</term>
<term>Madin Darby Canine Kidney Cells</term>
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<term>Mice</term>
<term>Mice, Inbred ICR</term>
<term>Orthomyxoviridae Infections (drug therapy)</term>
<term>Orthomyxoviridae Infections (metabolism)</term>
<term>Oseltamivir (pharmacology)</term>
<term>Oxidation-Reduction (drug effects)</term>
<term>Oxidative Stress (drug effects)</term>
<term>Superoxide Dismutase (metabolism)</term>
<term>Thiobarbituric Acid Reactive Substances (metabolism)</term>
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<term>Animaux</term>
<term>Antioxydants (pharmacologie)</term>
<term>Antiviraux (pharmacologie)</term>
<term>Association de médicaments ()</term>
<term>Cellules rénales canines Madin-Darby</term>
<term>Chiens</term>
<term>Infections à Orthomyxoviridae (métabolisme)</term>
<term>Infections à Orthomyxoviridae (traitement médicamenteux)</term>
<term>Inosine pranobex (pharmacologie)</term>
<term>Lignée cellulaire</term>
<term>Mâle</term>
<term>Oséltamivir (pharmacologie)</term>
<term>Oxydoréduction ()</term>
<term>Poumon (métabolisme)</term>
<term>Poumon (virologie)</term>
<term>Souris</term>
<term>Souris de lignée ICR</term>
<term>Sous-type H3N2 du virus de la grippe A ()</term>
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<term>Substances réactives à l'acide thiobarbiturique (métabolisme)</term>
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<term>Thiobarbituric Acid Reactive Substances</term>
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<term>Antiviral Agents</term>
<term>Ellagic Acid</term>
<term>Inosine Pranobex</term>
<term>Oseltamivir</term>
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<term>Oxidative Stress</term>
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<term>Substances réactives à l'acide thiobarbiturique</term>
<term>Superoxide dismutase</term>
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<term>Antioxydants</term>
<term>Antiviraux</term>
<term>Inosine pranobex</term>
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<term>Souris</term>
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<front><div type="abstract" xml:lang="en">Influenza pathogenesis comprises a complex cascade of impaired cellular processes resulting from the viral replication and exaggerated immune response accompanied by reactive oxygen species (ROS) burst and oxidative stress, destructing membranous structures and tissues. By classical virological and biochemical methods we compared and evaluated the therapeutic effects of 2.5mg/kg/day of the antiviral drug - oseltamivir (OS), 500mg/kg/day of the immune modulator - isoprinosine (IP) and 500mg/kg/day of the antioxidant agent ellagic acid (EA) with a focus on their combined activities in influenza H3N2 virus-infected mice. The survival, lung pathology and titers, as well as the oxidative stress biomarker thiobarbituric acid reactive substances (TBARS) in the lungs, liver and blood plasma, correlated to the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione reductase (GR) were assessed. We found that the viral inhibitor applied together with the immune modulator and the antioxidant exhibited strong therapeutic effects on the survival of the influenza-challenged mice. That effect was mostly pronounced for the triple combination - protection index (PI) of 75.2%, mean survival time (MST) extended by 5.8 days compared to the PBS control and significant reduction of the lung titers by 1.38 Δlg; 2.3 scores lower lung pathology and 8 times reduction of the accumulated TBARS in the lungs and liver on the 5<sup>-th</sup>
day p.i. The enzymatic assays revealed that this combination demonstrated very good protection against the damaging superoxide radicals (83% efficiency of SOD, in comparison to healthy controls 100%). The double combinations of OS with IP and EA also showed protective effects according to the virological analysis - PI of 53.1% and 54.5%. Ten times higher GR activity was observed when the combination EA+OS and monotherapy of EA were applied (96% in comparison to healthy controls 100%). The best antioxidant effect in blood plasma was observed in the EA+IP group - 4 times reduction in the TBARS-content compared to infected controls but it did not have any efficacy on the survival and lung injury.</div>
</front>
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<affiliations><list><country><li>Bulgarie</li>
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<name sortKey="Gegova, Galina A" sort="Gegova, Galina A" uniqKey="Gegova G" first="Galina A" last="Gegova">Galina A. Gegova</name>
<name sortKey="Simeonova, Lora S" sort="Simeonova, Lora S" uniqKey="Simeonova L" first="Lora S" last="Simeonova">Lora S. Simeonova</name>
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