Birutė Zablockienė1, Tomas Kačergius2,3, Arvydas Ambrozaitis4, Edvardas Žurauskas5, Maksim Bratchikov2, Laimutė Jurgauskienė6, Rolandas Zablockis4, Stefan Gravenstein3,7,8. 1. Clinic of Infectious and Chest Diseases, Dermatovenerology and Allergology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania Birute.Zablockiene@santa.lt. 2. Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 3. Department of Internal Medicine, Glennan Center for Geriatrics and Gerontology, Eastern Virginia Medical School, Norfolk, VA, U.S.A. 4. Clinic of Infectious and Chest Diseases, Dermatovenerology and Allergology, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 5. Department of Pathology, Forensic Medicine and Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 6. Clinic of Cardiovascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 7. Department of Medicine, Warren Alpert Medical School, School of Public Health, Brown University, and Providence Veterans Administration Hospital, Providence, RI, U.S.A. 8. Department of Health Services Policy and Practice, School of Public Health, Brown University, and Providence Veterans Administration Hospital, Providence, RI, U.S.A.
Abstract
BACKGROUND/AIM: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and expression of inducible nitric oxide synthase (iNOS), leading to overproduction of nitric oxide (NO). We studied whether zanamivir reduces pulmonary inflammation through inhibition of NO production in mice. MATERIALS AND METHODS: We treated IAV-infected mice daily with intranasal zanamivir. Controls were infected and either placebo-treated or untreated, or not infected and placebo-treated. Mice were weighed daily. After euthanasia on day 3, lungs were excised and bronchoalveolar lavage was performed and fluid nitrite concentration was determined. Lungs were analyzed microscopically. iNOS and IAV RNA levels in lungs were assessed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR). RESULTS: Mice undergoing zanamivir treatment had less weight loss, viral replication, and lung damage, as well as significant reductions of local NO and iNOS mRNA synthesis (p<0.05). CONCLUSION: Zanamivir is associated with an anti-inflammatory effect mediated through inhibition of NO production in IAV-infected mice. Copyright
BACKGROUND/AIM: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and expression of inducible nitric oxide synthase (iNOS), leading to overproduction of nitric oxide (NO). We studied whether zanamivir reduces pulmonary inflammation through inhibition of NO production in mice. MATERIALS AND METHODS: We treated IAV-infectedmice daily with intranasal zanamivir. Controls were infected and either placebo-treated or untreated, or not infected and placebo-treated. Mice were weighed daily. After euthanasia on day 3, lungs were excised and bronchoalveolar lavage was performed and fluid nitrite concentration was determined. Lungs were analyzed microscopically. iNOS and IAV RNA levels in lungs were assessed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR). RESULTS:Mice undergoing zanamivir treatment had less weight loss, viral replication, and lung damage, as well as significant reductions of local NO and iNOS mRNA synthesis (p<0.05). CONCLUSION:Zanamivir is associated with an anti-inflammatory effect mediated through inhibition of NO production in IAV-infectedmice. Copyright
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