Zanamivir Diminishes Lung Damage in Influenza A Virus-infected Mice by Inhibiting Nitric Oxide Production

• DOI: 10.21873/invivo.11263
• Publication Date: 2018-05-02T07:53:07Z
• Authors: Birutė Zablockienė; Rolandas Zablockis; Laimutė Jurgauskienė; Maksim Bratchikov; Arvydas Ambrozaitis; Edvardas Žurauskas; Tomas Kacergius; Stefan Gravenstein
• Keywords: 0303 health sciences; Time Factors; Histocytochemistry; Body Weight; Gene Expression; Nitric Oxide Synthase Type II; Viral Load; Nitric Oxide; Antiviral Agents; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Orthomyxoviridae Infections; Influenza A virus; Animals; Female; Zanamivir; Bronchoalveolar Lavage Fluid; Lung; Biomarkers

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.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).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).Zanamivir is associated with an anti-inflammatory effect mediated through inhibition of NO production in IAV-infected mice.