Efficiency of a medical product based on hypertonic sodium chloride (7%) and sodium hyaluronate (0.1%) in experimental pulmonary fibrosis model

Background. The pathogenesis of pulmonary fibrosis (both idiopathic and SARS-Cov-2-associated) is based on microdamages of the alveolar epithelium with impaired mechanisms of its regeneration. This leads to pathological re-epithelialization, fibroblast proliferation, and excess synthesis of extracellular matrix. As a result, the normal lung parenchyma is gradually replaced by fibrous tissue [1, 2]. The prevalence of idiopathic pulmonary fibrosis in the Russian Federation is about 8-12 cases per 100,000 population, and the incidence is 4-7 cases per 100,000 population [3]. Pulmonary fibrosis after COVID-19 may affect about a third of patients hospitalized with SARS-COV-2 [4-8]. Pirfenidone and nintedanib are the leading drugs considered as potentially effective in both idiopathic and post-COVID-19 pulmonary fibrosis. Pirfenidone is currently being studied as an antifibrotic agent after COVID-19 in an RCT [8]. However, nintedanib is produced only abroad, and both drugs are quite expensive, and their use may be associated with potential hepatotoxicity, which is especially undesirable, given the fact that liver dysfunction is common in patients infected with SARS-CoV-2 [9, 10]. Under these conditions, the search for new highly effective and safe compounds capable of preventing or resolving the development of pulmonary fibrosis is an urgent task. Thus, the use of hypertonic sodium solution in combination with hyaluronic acid, given its nonspecific antibacterial and antiviral properties, may be promising in the complex treatment of patients with SARS-CoV-2 infection. Objective. Evaluation of the effectiveness of a medical product based on hypertonic sodium chloride (7%) and sodium hyaluronate (0.1%) [Ingasalin® forte] on a model of bleomycin-induced pulmonary fibrosis. Methods. An experimental study was carried out on outbred male rats weighing 180-200 g (n=30). An experimental model of pulmonary fibrosis was created by a single intratracheal administration of bleomycin at a dose of 5 mg/kg [11]. A hypertonic sodium chloride (7%) and sodium hyaluronate (0.1%) [Inagasalin® forte 7%] was administered to animals daily (2 times a day) by inhalation using a Delphinus F1000 compressor nebulizer (Flaem Nuova, Italy) for 28 days. This route of administration corresponds to the route of administration of the test product in humans. Throughout the experiment, body weight was recorded weekly and clinical examination of animals was carried out in an open area. On the 30th day, blood samples were taken from animals of all groups for hematological analysis, followed by euthanasia and autopsy in order to register signs of changes in internal organs. The organs were fixed in 10% buffered formalin for histological examination. Results. It was found that the incidence of interstitial pneumonia was 3.3 times less common, the incidence of desquamative pneumonia was 2.5 less common, and the incidence of pulmonary fibrosis was 8 times less common in the group of therapy with the medical product Ingasalin® forte compared with the group without treatment. Conclusion. The medical product Ingasalin® forte minimizes the severity of interstitial-desquamative and fibrotic changes in the lungs, it can be recommended for further study as a mean for prevention and treatment of pulmonary fibrosis.

SARS-CoV-2, pulmonary fibrosis, SARS-CoV-2, Ingasalin® forte