A Dose-Dependent Study Examining Dexmedetomidine's Possible Effects Against Oxidative, Fibrotic, and Apoptotic Damage...

Objective: This study aimed to investigate the potential splenic tissue damage induced by radiotherapy (RT) and the potential protective effect of different doses of dexmedetomidine on this damage at the histopathological, immunohistochemical, and biochemical levels. Materials and Methods: In our study, Sprague Dawley rats were randomly divided into four groups: Control, Radiotherapy (RT; 8 Gy), RT + Dexmedetomidine 100 µg/kg (RT-D100), and RT + Dexmedetomidine 200 µg/kg (RT-D200). A single dose of 8 Gy radiotherapy was administered to each RT group. Spleen tissues were examined histologically with hematoxylin-eosin and immunohistochemically with anti-Caspase-3, anti-TGF-β1, and anti-TGF-β3 using light microscopy. TBARS and total thiol levels were also analyzed to assess oxidative stress and antioxidant capacity. Results: Histopathological results showed a significant decrease in white pulp diameter, decreased cellular density, and increased congestion in the red pulp in the RT group. Significant fibrosis, sinusoidal dilatation, vacuolization, and amyloid deposition were detected in the white pulp in the RT group. Regarding anti-caspase-3 immunoreactivity, strong positivity increased in the red pulp in the RT group, while a significant increase was observed in the white pulp in both the RT-D100 and RT groups. While the proportion of TGF-β1 immunopositive cells did not change significantly in the RT group, they increased significantly in both dexmedetomidine groups (especially RT-D200). TGF-β3 expression increased significantly only in the RT-D100 group. In biochemical analyses, TBARS levels increased significantly in the RT-D100 group. Total thiol levels decreased in the RT group and increased in the dexmedetomidine-treated groups. Conclusions: While RT caused histopathological damage and increased oxidative stress in spleen tissue, dexmedetomidine reduced this damage in a dose-dependent manner. The different immunohistochemical profiles of TGF-β1 and TGF-β3 suggest that these cytokines may have different functions in the spleen. 100 µg/kg dexmedetomidine stimulates a regenerative response through TGF-β3, while 200 µg/kg dexmedetomidine may provide immune regulation and antioxidative defense through TGF-β1.