The effect of aminoguanidine on acute lung injury induced by influenza A/H1N1/PDM09

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Abstract

Background. Acute lung injury is one of severe course of influenza infection with mortality up to 40% of patients, despite on etiological and pathogenetic therapy.

The aim of the article to study of the effects of aminoguanidine on correcting on acute lung injury induced by influenza virus A/California/7/09MA (mouse-adapted) (H1N1)pdm09, collection Smorodintsev Research Institute of Influenza.

Materials and methods. The study was performed on 95 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral infection at a dose of 1 LD50. The mortality was analysed. Levels of advanced glycation end-products (AGEs), proinflammatory cytokines in lung; saturation index and leukocytes marker parameters in blood; pathological and histological studies of lung were performed on 4 and 7 days post infection.

Results. Aminoguanidine led to 2-fold decrease in mortality in mice with virus-induced acute lung injury; significantly suppressed the growth of AGEs and proinflammatory cytokine levels in lung; reduced decrease of saturation index and hematological inflammatory markers; decreased level of inflammatory injury in lung tissue.

Conclusion. Aminoguanidine relieved virus-induced acute lung injury in mice. These AGEs inhibitor reduced the proinflammatory response and structural changes in respiratory tract epithelial cells induced by reactive carbonyl compounds on cell membrane.

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About the authors

Andrei G. Aleksandrov

Smorodintsev Research Institute of Influenza

Author for correspondence.
Email: forphchemistry@gmail.com
ORCID iD: 0000-0001-9212-3865

a graduate student in the Laboratory of Drug Safety

Russian Federation, Saint Petersburg

Tatiana N. Savateeva-Lyubimova

Smorodintsev Research Institute of Influenza

Email: drugs_safety@mail.ru
ORCID iD: 0000-0003-4516-3308

Professor, MD, PhD in Medicine, leading researcher in the Laboratory of Drug Safety

Russian Federation, Saint Petersburg

Kira I. Stosman

Smorodintsev Research Institute of Influenza; Institute of Toxicology of Federal Medico-Biological Agency

Email: labtox6@rambler.ru
ORCID iD: 0000-0001-7959-2376

PhD in Biology, senior researcher in the Laboratory of Drug Safety

Russian Federation, Saint Petersburg

Arman A. Muzhikyan

Smorodintsev Research Institute of Influenza

Email: vetdiagnostics.spb@gmail.com
ORCID iD: 0000-0002-7093-0014

PhD in Veterinary Sciences, leading researcher in the Laboratory of Drug Safety

Russian Federation, Saint Petersburg

Konstantin V. Sivak

Smorodintsev Research Institute of Influenza

Email: kvsivak@gmail.com
ORCID iD: 0000-0003-4064-5033
SPIN-code: 7426-8322
Scopus Author ID: 35269910300

PhD in Biology, Head of the Department of Preclinical Trials

Russian Federation, Saint Petersburg

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2. Fig. 1. Kaplan-Meier survival curve. * р ≤ 0,05 compared to group 1; # р ≤ 0,05 compared to group 2. Group 1 — intact mice; group 2 — infected mice treated with phosphate-buffered saline; group 3 — infected mice treated with aminoguanidine

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3. Fig. 2. Level of AGE in lung, estimated by fluorescence (AU/g). * р ≤ 0,05 compared to group1; # р ≤ 0,05 compared to group 2. Group 1 — intact mice, group 2 — infected mice treated with phosphate-buffered saline, group 3 — infected mice treated with aminoguanidine

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4. Fig. 3. Dynamics of saturation index during the experiment (Mean ± SE, %). * р ≤ 0,05 compared to group1; # р ≤ 0,05 compared to group 2. Group 1 — intact mice, group 2 — infected mice treated with phosphate-buffered saline, group 3 — infected mice treated with aminoguanidine

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5. Fig. 4. Proinflammatory cytokine level on 4th day post infection (Mean ± SE, pg/g). * р ≤ 0,05 compared to group 1; # р ≤ 0,05 compared to group 2. Group 1 — intact mice, group 2 — infected mice treated with phosphate-buffered saline, group 3 — infected mice treated with aminoguanidine

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6. Fig. 5. Proinflammatory cytokine level on 7th day post infection (Mean±SE, pg/g). * р ≤ 0,05 compared to group 1; # р ≤ 0,05 compared to group 2. Group 1 — intact mice, group 2 — infected mice treated with phosphate-buffered saline, group 3 — infected mice treated with aminoguanidine

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7. Fig. 6. Lung of mice during experiment. Hematoxylin-eosin stain. Magnification ×100. I — Lung of intact mouse; IIA and IIБ — Lung of infected mice treated with placebo on 4 (A) and 7 (Б) day post infection; IIIА и IIIБ — Lung of infected mice treated with aminoguanidine on 4 (A) and 7 (Б) day post infection. а — increased cellular infiltrate; b — thickening of the alveolar septum; c — vascular plethora of the lungs; d — the presence of atelectasis; e — “hepatization” pulmonary parenchyma; f — alveolar edema; g — the presence of red blood cells in the alveolar space

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