Effects of tyrosol on experimentally induced pulmonaryfibrosis in rats with bleomycin

Pulmonary fibrosis (PF) is a chronic progressive lung disease characterized by collagen increase and there is no effective treatment. Tyrosol, is a compound found in olive oil with antioxidant, anti-inflammatory and antifibrotic activity, and there are no publications on its effect on PF. The aim of this study is to investigate the dose-related effects of tyrosol on bleomycin (BLM)-induced PF in rats with pathological and biochemical parameters. In the study, 80 adult male rats will be used and they will be divided into eight groups, 10 animals in each group. In the first group, intratracheal (IT) saline will be applied and water will be given by gastric gavage during the experiment. Groups 2, 3, and 4 will receive tyrosol at doses of 20, 40, and 80 mg/kg, respectively, for 14 days by gastric gavage after the administration of IT saline. The 5th group will be administered 4mg/kg BLM IT. In the 6th, 7th and 8th groups, after a single dose of IT 4 mg/kg BLM, 20, 40 and 80 mg/kg doses of tyrosol will be administered by gastric gavage for 14 days, respectively. At the end of the experiment, animals will be euthanized by taking blood from the heart under anesthesia. Oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels will be determined from the blood serum taken. In addition, oxidative stress markers, interleukin 1 (IL-1), IL-6 IL-13, transforming growth factor beta (TGF beta), tumor necrosis factor alpha (TNF-alpha) levels from the bronchoalveolar lavage fluid (BALF) taken, will be measured by ELISA and cell morphologies will also be evaluated cytologically. After necropsy, the left lung lobe will be taken and the oxidative stress parameters and TNF α, IL-1, IL-6, IL-13, TGF-β, E-cadherin, α-SMA, vimentin, desmin, collagen Type I and Wnt. /β-cathenin levels will be measured by ELISA. For histopathological examinations, the right lung lobe will be evaluated for fibrosis by staining with Hematoxylin-Eosin and Masson's trichrome. In addition, the hydroxyproline (HPR) value, which is an indicator of the level of collagen in the lung tissue, will be measured with a spectrophotometer. Immunohistochemically, TNF α, IL-1, IL-6, IL-13, TGF-β, E-cadherin, α-SMA, vimentin, desmin, collagen Type I and Wnt/β-cathenin antibodies were stained with streptavidin-biotin peroxidase technique. All findings will be evaluated statistically.