Effect of baricitinib on renal injury in sepsis model induced by cecal ligation and puncture in rats

Sepsis, caused by an uncontrolled host response to infection, is a major health problem leading to organ dysfunction and death. Sepsis remains the most important cause of acute kidney injury in the intensive care unit. The effects of the JAK/STAT signaling pathway, which regulates the signaling of various cytokines and growth factors, on inflammation and immune regulation have been demonstrated in many different studies. As a result of the studies, it has been understood that JAK2/STAT3 signaling pathway plays a role in sepsisinduced kidney injury. In this thesis, we investigated the effects of JAK1 and JAK2 inhibitor baricitinib on kidney damage in sepsis model induced by cecal ligation and puncture (CLP) in rats. 40 male Straque Dawley rats were used in our study. The rats were divided into 4 groups of 10 animals per group (Group 1: Sham, Group 2: CLP, Group 3: CLP + 3 mg/kg Baricitinib, Group 4: CLP + 10 mg/kg Baricitinib). The cecum of the CLP-treated groups was tied with a thread and punctured with a 21 gauge needle to spread the fecal contents into the abdominal cavity. The animals were sacrificed 24 hours after the abdominal region was sutured closed. The treatment groups received 2 different doses of baricitinib by oral gavage 45 minutes before the CLP model was established. Blood samples were taken and sera were obtained. BUN, sCr, TNF-α, IL-1β, IL-18 levels were analyzed by ELISA method. Kidneys of the animals were removed for histopathologic examination. Serum BUN, sCr, TNF-α, IL-1β, IL-18 levels showed a statistically significant increase in the CLP group compared to the control group (p0,05). Increased serum BUN, sCr, TNF-α, IL-1β, IL-18 levels in CLP group showed a statistically significant decrease in both 3 mg/kg and 10 mg/kg baricitib treated groups (p0,05). Histopathologic examinations showed that kidney damage occurred in the CLP group compared to the control group (p0,05). Histopathologic damage in the kidney tissue in the CLP group showed a statistically significant decrease in the baricitinib 3 mg/kg and 10 mg/kg groups (p0,05). In this thesis, we found that 2 different doses of baricitinib (3 mg/kg and 10 mg/kg) showed protective properties by reducing inflammation and kidney damage in CLP-induced experimental sepsis model.