Investigation of the effect of pentoxifylline on HIF-1ALPHA gene expression and serum HIF-1α levels in irradiated rats

One of these complications is radiation-induced fibrosis. Radiation-induced fibrosis, which can develop in cases treated with radiotherapy in head and neck cancers, has many negative, progressive symptoms that reduce the quality of life and can also be encountered in dental practices such as trismus.In our study, it was planned to evaluate the preventive/therapeutic efficacy of pentoxifylline against hypoxic damage in tissues in rats with irradiation-induced fibrosis model, based on HIF-1α gene expression level and accompanying histopathological findings. 17 male Sprague Dawley rats used in our study were divided into 3 groups. The first group is the experimental group (R) that only received radiotherapy, and the second group is the experimental group (PR), which is administered oral pentoxifylline for 24 days after radiotherapy. The third group is the control group (K) consisting of 5 completely healthy rats. Oral pentoxifylline was given to 3 rats randomly selected from the control group for 24 days (K (+)). A single dose of 90Gy equivalent radiotherapy was administered to the experimental groups under anesthesia. Oral pentoxifylline was given to the PR and K (+) groups for prophylactic purposes, while we expected fibrosis to develop following radiotherapy. At the end of the 24th day, the groups were sacrificed and tissue samples were taken from M.rectus femoris muscles exposed to radiation along with blood samples. ELISA was studied for HIF-1 gene expression in blood samples; histopathological findings and Real-Time PCR findings were also evaluated in tissue samples. In histopathological examinations, it was determined that radiation-induced fibrosis started to form, but its maturation was not fully realized. Although Real-Time PCR findings of HIF-1α gene expression could not reach statistical significance, it was concluded that there was a positive correlation between developing fibrosis and HIF-1α expression. It has also been observed that pentoxifylline has positive effects on radiation-induced fibrosis. Our study shows that pentoxifylline offers the opportunity to limit radiation-induced fibrosis. Key Words: Pentoxifylline, Fibrosis, Radiation Induced Fibrosis, HIF-1α, Radiotherapy This study was supported by Istanbul University Scientific Research Projects Unit. Project No: 2020-36622.