Pancreatic toxicity of influenza A/H1N1-California virus infection in mice at the background of hyperglycemia induced by streptozotocin administration

Abstract

Particular attention in the study of comorbid conditions is paid to viral diseases, in particular, those caused by the pandemic influenza virus type A subtype H1N1, as one of the most pathogenic and contagious. Investigation of the effect of this virus in the development of diabetes mellitus will make it possible to more effectively carry out preclinical studies to find the most effective methods of treating a viral infection against the background of a pre-existing somatic pathology. Purpose of the study was to evaluate the pancreatic toxicity effect of exposure to influenza A/H1N1-California virus in the development of streptozotocin diabetes in DBA/2 and BALB/c mice. Material and methods. Groups of mice DBA/2 (n = 36) and BALB/c (n = 58) were formed: infected with influenza A/H1N1-California virus (at different doses); with the introduction of a solution of streptozotocin at a dose of 150 mg / kg; with the combined use of agents. Life expectancy, blood glucose and insulin level, pathomorphological changes in the pancreas were assessed. Results and discussion. The death of animals was observed only in mice of the DBA/2 line: with the introduction of streptozotocin – 12.5 %, with intranasal infection with the virus (at a dose of 5.7 lg TCID50) – 80 %, with combined exposure – 78 %. A comparative study of mice of the DBA/2 and BALB/c lines showed the possibility of using mice of both lines to study the combined effect of influenza A/H1N1 virus and experimental diabetes, taking into account the dose of infection. Infection of BALB/c mice caused the formation of morphological changes only in the exocrine part of the pancreas. In mice of both lines, after the administration of streptozotocin, persistent hyperglycemia was formed, and pathomorphological changes in the pancreas were recorded mainly in the endocrine part. Similar changes in the pancreas, but more severe, involving the exocrine zone, were found during subsequent infection: in mice of the DBA/2 line in the form of a focal disorder of the acinar structure with degeneration of acinocytes and a compensatory regenerative reaction of cells in intact areas; in mice of the BALB/c line in the form of more significant damage to the ductal system than in DBA/2 with the formation of powerful periductal fibrosis and mononuclear infiltrates. Conclusions. A comparative study showed that DBA/2 mice had more pronounced changes in both the exocrine and endocrine apparatus of the pancreas when infected with influenza A/H1N1-California virus and experimental diabetes mellitus.