ANTIOXIDANTS, cilt.14, sa.10, ss.1-16, 2025 (SCI-Expanded)
Objective: This study was conducted to evaluate the potential radioprotective and therapeutic effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor (α2AR) agonist, against ionizing X-ray-induced small intestinal injury in a dose-dependent manner. Methods: Male Sprague Dawley rats were randomly categorized into four groups. These groups were the Control, Ionizing Radiation (IR, 8 Gy X-ray), IR+DEX 100 µg/kg, and IR+DEX 200 µg/kg. DEX was administered intraperitoneally to the treatment groups 30 min before radiation exposure. All groups were sacrificed 24 h following irradiation. Firstly, the small intestinal tissues were evaluated histopathologically (H&E staining). Subsequently, levels of malondialdehyde (MDA) and glutathione (GSH), as markers of oxidative stress, were measured, and immunohistochemical expression of Caspase-3 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) was analyzed. Results: In the IR group, significant histopathological alterations were observed, including villus atrophy and villus loss due to fusion, crypt loss, and mucosal degeneration. Additionally, there was an increase in MDA levels, a decrease in GSH levels, and a marked elevation in the expression of Caspase-3 and 8-OHdG. In the DEX-treated groups, particularly at the 200 µg/kg dose, significant improvements were noted in these parameters. It was determined that the histological architecture was largely preserved, oxidative stress was reduced, and apoptosis was suppressed. Conclusion: The findings suggest that DEX may effectively reduce X-ray-induced small intestinal injury in a dose-dependent manner, and that this effect is mediated through antioxidant and anti-apoptotic mechanisms. DEX holds potential for the prevention or treatment of radiation-induced gastrointestinal toxicities.