Possible therapeutic effect of ramelteon in rats with radiation-induced brain injury

Radiotherapy (RT) is one of the most commonly used treatment methods in cancer treatment. In patients, receiving RT, there may be results starting with headache in acute period and ending with dementia and death in late period. The ionizing radiation can cause cellular damage in and adjacent brain tissue by inducing the production of intracellular reactive oxygen species and proinflammatory cytokines in the central nervous system. Ramelteon (RML) is a melatonin receptor agonist having anti-inflammatory and antioxidant effects. In this study, it was aimed to investigate the possible therapeutic effect of RML in brain damage, induced by 10 Gray radiation. A total of 32 Wistar Albino female rats were used in the study, including the control group, the radiation group, the radiation plus RML group, and the RML group alone, with 8 rats in each group. At the end of the study, hemogram measurement was performed from blood samples taken from rats. Histopathologically hematoksilen-eozin (H-E) staining was performed to observe brain damage taken from the cortex regions of one hemisphere of the isolated brain tissues. Total oxidant status (TOS) and total antioxidant status (TAS) and oxidative stress ındex (OSI) were studied to measure oxidative stress levels. In addition, tumor necrosis factor-α (TNF-α), caspase-3, caspase-9 and ınterleukin-10(IL-10) levels were measured and evaluated by ELISA method. According to the histological examination results, edema, vacuolization and apoptotic bodies were more common in the radiation groups compared to the control group. However, it was observed that this appearance was significantly reduced in the RML group, and cell integrity was preserved. It was observed that OSI, which increased after radiation application compared to the control group, decreased significantly (p<0.0001) with RML treatment. Compared to the control group; It was determined that TNF-α value increased in the radiation-treated groups and decreased significantly with RML treatment (p<0.0001). Although IL-10 level decreased significantly in the radiation-treated group compared to the control group (p=0.003), it increased significantly in the RML-treated group (p<0.0001). It was observed that caspase-3 and caspase-9 levels increased after radiation application compared to the control group, and this increase was significantly decreased with RML treatment (p<0.0001). These results have been shown that RML may have a protective and therapeutic role in radiotoxicity-induced brain damage with its anti-inflammatory, antiapoptotic and antioxidative effects. Keywords: Radiation, Brain Injury, Ramelteon, Oxidative Stress, Inflammation, Apoptosis