[Assessment of histological changes in the lungs and Bax and Bcl-2 expression in bronchial epithelium, alveolar type 1 cells and neutrophils of rats in poisoning with baclofen].

Objective: To study the histological changes in lung of rats, evaluate their dynamics and determine the Bax and Bcl-2 genes expression in bronchial epithelium, alveolar type 1 cells and neutrophils at different times after the administration of baclofen.

Material and methods: The experiment was conducted on 20 mature (at the age of 20 weeks) male Wistar rats with a mass of 290-350 g, distributed in 4 groups (5 rats in each). Animals in the control group did not receive baclofen. Rats in experimental groups received baclofen at a dose of 85 mg/kg: in the 1st group, the experiment duration was 3 hours (time to maximum observed blood drug concentration); in the 2nd group - 4.5 h (drug half-life and time to maximum observed concentration of the main drug's metabolite - beta-[p-chlorophenyl])-gamma-hydroxybutyric acid in the blood); in the 3rd group - 24 h.

Results: A complex of pathological reactions developed in lungs of experimental animals when baclofen muscle relaxant was administered, namely circulatory disturbances at all levels of the microvasculature (venular and capillary congestion, hemorrhages in the interalveolar septums, alveoli, sludge), emphysema, sites of which punctuated with atelectases and dystelectases. The complex of pathological changes in the lungs had a certain dynamics and reached its highest severity by the 24th hour. Bax expression was strong, while Bcl-2 expression was moderate in the immunohistochemical (IHC) study of bronchical epithelium and alveolar type 1 cells, Bax and Bcl-2 expression in neutrophils was moderate in rats of the 1st group. The expression of Bax and Bcl-2 was strong in the bronchial epithelium and alveolar type 1 cells, the expression of Bax in neutrophils was moderate, and BCL-2 - strong in animals of the 2nd group. The expression of Bax in bronchial epithelium and alveolar type 1 cells was moderate, expression of Bcl-2 in bronchial epithelium and alveolar type 1 cells - strong, expression of Bax in neutrophils - weak and expression of Bcl-2 - strong among the rats of the 3rd group.

Conclusion: The complex of pathological changes in lungs had a certain dynamic. Data on the histological changes in lungs in combination with the results of the chemical study, can be used to diagnose the poisoning by baclofen and to establish the time since the drug was administered. The results obtained during the IHC study suggest the involvement of apoptosis in the development of lesion of bronchial epithelium and alveolar type 1 cells. In addition, the expression of Bcl-2 in epithelial cells may play a role in the process of their regeneration.