The effect methylglyoxal on acute lung injury induced by influenza A(H1N1)PDM09 in mice

Cover Page
Open Access Open Access
Restricted Access Subscription Access

Abstract


The aim of the article. To study of the effect of 2-oxopropanal (methylglyoxal) on virus-induced acute lung injury.

Materials and methods. The study was performed on adult female outbred mice. Methylglyoxal administered subcutaneously at a dose of 50 mg/kg/day to mice for 14 days prior to infection. The pandemic influenza virus A(H1N1)pdm09 was used for modeling viral infection at a dose of 0.75 LD50. Hematology, pathomorphological and histological studies were performed on 4, 7 and 14 days post infection. Level of lung injury was performed by semi-quantitative method.

Results. Methylglyoxal induced 2-fold increase of mortality and lung lesion area (р < 0.05). The structural changes in lung tissue had inflammatory character. These changes had progressive character. The ratio of neutrophiles/lymphocytes was increased by 2.5 times on average in infected animals (р < 0.05 compared to intact animals).

Conclusion. Methylglyoxal aggravated acute lung injury in mice by inducing structural changes in tissue and increased mortality level.


Andrei G. Aleksandrov

Smorodintsev Research Institute of Influenza

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

Russian Federation, Saint Petersburg

a graduate student in the Laboratory of Drug Safety

Tatiana N. Savateeva-Lyubimova

Smorodintsev Research Institute of Influenza

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

Russian Federation, Saint Petersburg

Professor, MD, PhD in Medicine, Leading Researcher in the Laboratory of Drug Safety

Arman A. Muzhikyan

Smorodintsev Research Institute of Influenza

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

Russian Federation, Saint Petersburg

PhD in Veterinary Sciences, Leading Researcher in the Laboratory of Drug Safety

  1. Грипп у взрослых: методические рекомендации по диагностике, лечению, специфической и неспецифической профилактике / Под ред. А.Г. Чучалина, Т.В. Сологуб. – СПб.: НП-Принт, 2014. – 192 с. [Gripp u vzroslykh: metodicheskie rekomendatsii po diagnostike, lecheniyu, spetsificheskoy i nespetsificheskoy profilaktike. Ed. by A.G. Chuchalin, T.V. Sologub. Saint Petersburg: NP-Print; 2014. 192 p. (In Russ.)]
  2. Киселев О.И. Пандемии начала XXI века. Грипп птиц и пандемия «свиного» гриппа H1N1 2009 г. – СПб.: Фолиант, 2016. – 368 с. [Kiselev OI. Pandemii nachala XXI veka. Gripp ptits i pandemiya “svinogo” grippa H1N1 2009 g. Saint Petersburg: Foliant; 2016. 368 p. (In Russ.)]
  3. Чурляев Ю.А., Вереин М.Ю., Кан С.Л., и др. Острый респираторный дистресс-синдром при тяжелой черепно-мозговой травме // Общая реаниматология. – 2009. – Т. 5. – № 2. – С. 21–26. [Churlyaev YA, Verein MY, Kan SL, et al. Acute respiratory distress syndrome in severe brain injury. General Reanimatology. 2009;5(2):21-26. (In Russ.)]. https://doi.org/10.15360/1813-9779-2009-2-21.
  4. Фастова И.А., Губанова Е.И. Синдром острого повреждения легких при экспериментальном перитоните // Вестник новых медицинских технологий. – 2012. – Т. 19. – № 2. – С. 114–117. [Fastova IA, Gubanova EI. Acute lungs injury syndrome in experimental peritonitis. Journal of new medical technologies. 2012;19(2):114-117. (In Russ.)]
  5. Росстальная А.Л., Сабиров Д.М., Акалаев Р.Н., и др. Острое повреждение легких: спорные вопросы и нерешенные проблемы (обзор литературы) // Журнал им. Н.В. Склифосовского Неотложная медицинская помощь. – 2016. – № 3. – С. 66–72. [Rosstalnaya AL, Sabirov DM, Akalaev RN, et al. Acute lung injury: issues and remaining challenges (a literature review). Neotlozhnaia meditsinskaia pomoshch’. 2016;(3):66-72. (In Russ.)]
  6. Short KR, Kroeze EJBV, Fouchier RAM, Kuiken T. Pathogenesis of influenza-induced acute respiratory distress syndrome. Lancet Infect Dis. 2014;14(1):57-69. https://doi.org/10.1016/s1473-3099(13)70286-x.
  7. Kim KM, Jung DH, Jang DS, et al. Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: a possible pathway through the induction of heme oxygenase-1 expression. Toxicol Appl Pharmacol. 2010;244(2):106-113. https://doi.org/10.1016/j.taap.2009.12.023.
  8. Byun K, Yoo Y, Son M, et al. Advanced glycation end-products produced systemically and by macrophages: A common contributor to inflammation and degenerative diseases. Pharmacol Ther. 2017;177:44-55. https://doi.org/10.1016/j.pharmthera.2017.02.030.
  9. Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001;44(2):129-146. https://doi.org/10.1007/s001250051591.
  10. Балаболкин М.И. Роль гликирования белков, окислительного стресса в патогенезе сосудистых осложнений при сахарном диабете // Сахарный диабет. – 2002. – Т. 5. – № 4. – С. 8–16. [Balabolkin MI. Rol’ glikirovaniya belkov, okislitel’nogo stressa v patogeneze sosudistykh oslozhneniy pri sakharnom diabete. Diabetes mellitus. 2002;5(4):8-16. (In Russ.)]. https://doi.org/10.14341/DM200248-16.
  11. Ahmed N, Thornalley PJ. Роль конечных продуктов гликирования в патогенезе осложнений сахарного диабета // РМЖ. – 2009. – Т. 17. – № 9. – С. 642–650. [Ahmed N, Thornalley PJ. Rol’ konechnykh produktov glikirovaniya v patogeneze oslozhneniy sakharnogo diabeta. RMZh. 2009;17(9):642-650. (In Russ.)]
  12. Подачина С.В. Роль блокаторов конечного гликирования белков в формировании неврологических осложнений сахарного диабета // Фарматека. – 2011. – № 16. – С. 37–42. [Podachina SV. Role of glycation end-products blockers in the development of neurologic complications of diabetes mellitus. Farmateka. 2011;(16):37-42. (In Russ.)]
  13. Спасов A.A., Соловьева О.А., Кузнецова В.А. Гликирование белков при сахарном диабете и возможности его фармакологической коррекции (обзор) // Химико-фармацевтический журнал. – 2017. – Т. 51. – № 6. – C. 3–7. [Spasov AA, Solov’eva OA, Kuznetsova VA. Protein glycation during diabetes mellitus and the possibility of its pharmacological correction (Review). Pharmaceutical chemistry journal. 2017;51(6):3-7. (In Russ.)]
  14. Урбах В.Ю. Статистический анализ в биологических и медицинских исследованиях. – М.: Медицина, 1975. – 296 с. [Urbakh VY. Statisticheskiy analiz v biologicheskikh i meditsinskikh issledovaniyakh. Moscow: Meditsina; 1975. 296 p. (In Russ.)]
  15. Ожередова Н.А., Веревкин М.Н., Светлакова Е.В. Общая вирусология: Методические указания. – Ставрополь: АГРУС, 2013. – 50 с. [Ozheredova NA, Verevkina MN, Svetlakov EV. Obshchaya virusologiya: Metodicheskie ukazaniya. Stavropol’: AGRUS; 2013. 50 p. (In Russ.)]
  16. Golej J, Hoeger H, Radner W, et al. Oral administration of methylglyoxal leads to kidney collagen accumulation in the mouse. Life Sci. 1998;63(9):801-807. https://doi.org/10.1016/s0024-3205(98)00336-1.
  17. Matute-Bello G, Downey G, Moore BB, et al. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44(5):725-738. https://doi.org/10.1165/rcmb.2009-0210ST.
  18. Preusse M, Schughart K, Wilk E, et al. Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains. BMC Res Notes. 2015;8:225. https://doi.org/10.1186/s13104-015-1195-8.
  19. Di Loreto S, Caracciolo V, Colafarina S, et al. Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1beta and nerve growth factor in cultured hippocampal neuronal cells. Brain Res. 2004;1006(2):157-167. https://doi.org/10.1016/j.brainres.2004.01.066.
  20. Baig MH, Jan AT, Rabbani G, et al. Methylglyoxal and Advanced Glycation End products: Insight of the regulatory machinery affecting the myogenic program and of its modulation by natural compounds. Sci Rep. 2017;7(1):5916. https://doi.org/10.1038/s41598-017-06067-5.

Supplementary files

Supplementary Files Action
1. Fig. 1. Percent survival during experiment. 1st group — intact mice, 2nd group — infected mice treated with NaCl 0.9%, 3rdgroup — infected mice treated with methylglyoxal. * р > 0,05 compared to intact mice, # р > 0,05 compared to infected mice treated with NaCl 0.9% View (48KB) Indexing metadata
2. Fig. 2. Lung parenchyma of mice. Hematoxylin and eosin staining, magnification ×40 and ×400. a — intact mice; b — 2nd group on 4th day; c — 3rd group on 4th day; d — 2nd group on 7th day; e — 3rd group on 7th day; f — 2nd group on 14th day; g — 3rd group on 14th day View (1MB) Indexing metadata
3. Fig. 2. Lung parenchyma of mice. Hematoxylin and eosin staining, magnification ×40 and ×400. a — intact mice; b — 2nd group on 4th day; c — 3rd group on 4th day; d — 2nd group on 7th day; e — 3rd group on 7th day; f — 2nd group on 14th day; g — 3rd group on 14th day View (460KB) Indexing metadata

Views

Abstract - 40

PDF (Russian) - 0

Cited-By


PlumX

Refbacks

  • There are currently no refbacks.

Copyright (c) 2019 Aleksandrov A.G., Savateeva-Lyubimova T.N., Muzhikyan A.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.