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- MakaleYayıncıda açık erişim2025Could Different Doses of Dexmedetomidine Be as Effective as Amifostine Against Radiotherapy-Induced Liver Injury in Rats? Evidence from Mitotic, Apoptotic, Oxidative, and Neurogenic Insights
Beyazal Polat, Hatice; Yilmaz, Hamit; Demir, Kasim; Kilinc, Kagan; Gülhan, Belemir; Rakici, Sema Yilmaz; Tumkaya, Levent
Background/Objectives: Radiotherapy (RT) induces oxidative stress and structural damage in solid tissues, including the liver. This study aimed to investigate the histological and immunohistochemical effects of dexmedetomidine (DEX) and amifostine on their potential protective and regenerative properties against liver injury induced by radiation therapy. Methods: This study consisted of five randomized groups: control, RT, RT-D100, RT-D200, and RT-A (Amifostine). A total of 100 mu g/kg DEX, 200 mu g/kg DEX, and 200 mu g/kg amifostine were administered before radiotherapy as per the experimental design. After RT, liver specimens were analyzed for histological alterations, including periportal and perisinusoidal fibrosis, vacuolization, and pyknotic nuclei. Furthermore, immunohistochemistry investigations were conducted to evaluate apoptosis, mitosis, oxidative stress, and neural regeneration in non-neuronal liver tissue following radiotherapy and subsequent treatment. Results: The control group's liver tissue exhibited standard histological architecture, whereas the RT group displayed severe cellular degeneration, periportal and perisinusoidal fibrosis, cytoplasmic vacuolization, and an increase in pyknotic nuclei. The apoptotic index was markedly reduced in the RT-D100 and RT-D200 groups relative to the RT group. Furthermore, caspase-3 immunoactivity was negligible in the control group, while a significant increase was observed in the RT group. The administration of amifostine significantly increased GAP-43 levels. Conclusions: DEX mitigates RT-induced hepatic injury chiefly through antioxidant and anti-apoptotic pathways, whereas amifostine promotes hepatic regeneration by modulating GAP-43.
- MakaleAçık Erişim2025A Dose-Dependent Study Examining Dexmedetomidine's Possible Effects Against Oxidative, Fibrotic, and Apoptotic Damage Induced by Radiation Exposure in Spleen Tissue
Beyazal Polat, Hatice; Yilmaz, Hamit; Kilinc, Kagan; Gülhan, Belemir; Yilmaz Rakici, Sema; Tümkaya, Levent
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 mu g/kg (RT-D100), and RT + Dexmedetomidine 200 mu g/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-beta 1, and anti-TGF-beta 3 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-beta 1 immunopositive cells did not change significantly in the RT group, they increased significantly in both dexmedetomidine groups (especially RT-D200). TGF-beta 3 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-beta 1 and TGF-beta 3 suggest that these cytokines may have different functions in the spleen. 100 mu g/kg dexmedetomidine stimulates a regenerative response through TGF-beta 3, while 200 mu g/kg dexmedetomidine may provide immune regulation and antioxidative defense through TGF-beta 1.