Activation of Caspase-Induced Apoptosis and the Reaction of Parotid Salivary Gland Mast Cells After a Single Oral Administration

Depleted uranium has high cumulative capacity and, upon entering the human body, exerts radiological and chemotoxic effects. The aim of the study was to immunohistochemically evaluate the activity of caspase-3 and -9, as well as the response of stromal mast cells in the parotid salivary gland at 1, 3, and 6 months after a single oral administration of an aqueous solution of depleted uranium oxides. Material and methods. The experiment was conducted on 180 outbred male white rats divided into 6 groups (3 experimental and 3 control). Animals in the experimental groups received a single oral dose of depleted uranium (0.01 mg/100 g body weight). The parotid glands of control and experimental groups were examined after 1, 3, and 6 months. Organs were fixed in 10% neutral formalin, followed by histological staining (hematoxylin-eosin), immunohisto- chemical detection of caspases-3 and -9, and identification of mast cells (tryptase⁺, ChAE⁺). Results. At 1 month after depleted uranium administration, ultrastructural changes in acinar cells (vacuolization, protein dystrophy) and stromal inflammatory reactions (edema, vascular congestion) were observed. Immunohistochemical analysis revealed a significant increase in caspase-9 activity in the parenchyma, while caspase-3 expression increased significantly only by the 3rd month. By the 6th month, caspase-induced apoptosis in the parenchyma decreased but persisted in ductal cells. Mast cells showed peak activity at 1 month (increased tryptase⁺ and ChAE⁺ cells), followed by a decline in functional activity by the 6th month. Conclusion. Oral intake of depleted uranium oxides induces a biphasic response in the parotid gland: an early phase (1 month) involves acute damage with activation of the mitochondrial apoptosis pathway (caspase-9) and mast cell degranulation, while a late phase (3–6 months) transitions to chronic inflammation with predominant caspase-3-dependent apoptosis in the ducts. These findings enhance the understanding of depleted uranium toxicity mechanisms, highlighting the role of stromal-parenchymal interactions in long-term salivary gland damage.

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