Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model.
Identifieur interne : 000948 ( PubMed/Curation ); précédent : 000947; suivant : 000949Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model.
Auteurs : P. Ghezzi [Italie] ; D. UngheriSource :
- International journal of immunopathology and pharmacology [ 0394-6320 ]
Descripteurs français
- KwdFr :
- Acétylcystéine (usage thérapeutique), Animaux, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (mortalité), Infections à Orthomyxoviridae (traitement médicamenteux), Modèles animaux de maladie humaine, Mâle, Ribavirine (usage thérapeutique), Souris, Synergie des médicaments, Taux de survie, Virus de la grippe A (), Virus de la grippe A (immunologie).
- MESH :
- immunologie : Virus de la grippe A.
- mortalité : Infections à Orthomyxoviridae.
- traitement médicamenteux : Infections à Orthomyxoviridae.
- usage thérapeutique : Acétylcystéine, Ribavirine.
- Animaux, Infections à Orthomyxoviridae, Modèles animaux de maladie humaine, Mâle, Souris, Synergie des médicaments, Taux de survie, Virus de la grippe A.
English descriptors
- KwdEn :
- Acetylcysteine (therapeutic use), Animals, Disease Models, Animal, Drug Synergism, Influenza A virus (drug effects), Influenza A virus (immunology), Male, Mice, Orthomyxoviridae Infections (drug therapy), Orthomyxoviridae Infections (mortality), Orthomyxoviridae Infections (prevention & control), Ribavirin (therapeutic use), Survival Rate.
- MESH :
- chemical , therapeutic use : Acetylcysteine, Ribavirin.
- drug effects : Influenza A virus.
- drug therapy : Orthomyxoviridae Infections.
- immunology : Influenza A virus.
- mortality : Orthomyxoviridae Infections.
- prevention & control : Orthomyxoviridae Infections.
- Animals, Disease Models, Animal, Drug Synergism, Male, Mice, Survival Rate.
Abstract
Oxidative stress is implicated in the pathogenesis of pulmonary damage during viral infections. In a previous study we observed a significant improvement of survival of influenza-infected mice with NAC, 1g/kg divided in two daily administrations, for 8 days including a pretreatment on day 1 before infection. In order to test NAC in a more realistic model, we studied the effect of combined treatment with NAC and the antiviral drug, ribavirin. Since in the present work we wanted to test a possible synergistic effect by combination of NAC and ribavirin, we used a different NAC's treatment regimen (1 g/kg, once a day for 4 days) that, alone, did not significantly protect mice from death. Mice (12 per group) infected intranasally with a lethal dose of influenza A virus APR/8. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h after infection and until day 4 after infection, in association with ribavirin (100 mg/kg, i.p.). End-point evaluation was 14-day survival. With this schedule survival in infected mice was 17%, it was not significantly changed by NAC (25%). Survival increased to 58% with ribavirin and to 92% (n=12) with a combined treatment with ribavirin and NAC. This suggest that antioxidant therapy can increase survival by either improving the defenses against virus or by protecting from the pathogenesis of lung inflammation.
DOI: 10.1177/039463200401700114
PubMed: 15000873
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Ghezzi</name><affiliation wicri:level="1"><nlm:affiliation>Mario Negri Institute, Milan, Italy. ghezzi@marionegri.it</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Mario Negri Institute, Milan</wicri:regionArea></affiliation></author><author><name sortKey="Ungheri, D" sort="Ungheri, D" uniqKey="Ungheri D" first="D" last="Ungheri">D. 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In a previous study we observed a significant improvement of survival of influenza-infected mice with NAC, 1g/kg divided in two daily administrations, for 8 days including a pretreatment on day 1 before infection. In order to test NAC in a more realistic model, we studied the effect of combined treatment with NAC and the antiviral drug, ribavirin. Since in the present work we wanted to test a possible synergistic effect by combination of NAC and ribavirin, we used a different NAC's treatment regimen (1 g/kg, once a day for 4 days) that, alone, did not significantly protect mice from death. Mice (12 per group) infected intranasally with a lethal dose of influenza A virus APR/8. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h after infection and until day 4 after infection, in association with ribavirin (100 mg/kg, i.p.). End-point evaluation was 14-day survival. With this schedule survival in infected mice was 17%, it was not significantly changed by NAC (25%). Survival increased to 58% with ribavirin and to 92% (n=12) with a combined treatment with ribavirin and NAC. This suggest that antioxidant therapy can increase survival by either improving the defenses against virus or by protecting from the pathogenesis of lung inflammation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">15000873</PMID><DateCompleted><Year>2004</Year><Month>10</Month><Day>22</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>14</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0394-6320</ISSN><JournalIssue CitedMedium="Print"><Volume>17</Volume><Issue>1</Issue><PubDate><MedlineDate>2004 Jan-Apr</MedlineDate></PubDate></JournalIssue><Title>International journal of immunopathology and pharmacology</Title><ISOAbbreviation>Int J Immunopathol Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model.</ArticleTitle><Pagination><MedlinePgn>99-102</MedlinePgn></Pagination><Abstract><AbstractText>Oxidative stress is implicated in the pathogenesis of pulmonary damage during viral infections. In a previous study we observed a significant improvement of survival of influenza-infected mice with NAC, 1g/kg divided in two daily administrations, for 8 days including a pretreatment on day 1 before infection. In order to test NAC in a more realistic model, we studied the effect of combined treatment with NAC and the antiviral drug, ribavirin. Since in the present work we wanted to test a possible synergistic effect by combination of NAC and ribavirin, we used a different NAC's treatment regimen (1 g/kg, once a day for 4 days) that, alone, did not significantly protect mice from death. Mice (12 per group) infected intranasally with a lethal dose of influenza A virus APR/8. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h after infection and until day 4 after infection, in association with ribavirin (100 mg/kg, i.p.). End-point evaluation was 14-day survival. With this schedule survival in infected mice was 17%, it was not significantly changed by NAC (25%). Survival increased to 58% with ribavirin and to 92% (n=12) with a combined treatment with ribavirin and NAC. 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