The role of selenium in reducing urografin-induced oxidative stress–related renal injury: Investigation of TNF-α, Caspase-3, and Nrf2/Keap1/HO-1 gene expressions

The kidney, ureters, bladder and urethra are the fundamental anatomical components of the urinary system. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography play a critical role in the detailed evaluation of urinary system and in the diagnosis of its pathologies. Urografin, an ionic and high-osmolar contrast agent frequently used in radiological imaging causes damage to kidney tissue primarily by inducing oxidative stress. This damage is associated with inflammatory, apoptotic and oxidative stress-related pathways, including TNF- α and Caspase-3. Selenium, a trace element found in the structure of glutathione peroxidase, plays a key role in the body's antioksidant defense mechanisms. This study investigates the role of selenium in reducing oxidative stress-related renal damage that develops following urografin administration in rats, by examining TNF- α, Caspase-3 and Nrf2/Keap1/HO-1 gene expressions. In a 7 day experimental contrast nephropathy model, rats were divided into four groups; Control, URO, URO+SE, SE (n:8 in each group) and treatments were administered under conditions of equal stress. Tissues were evaluated histopathologically using hematoxylin and eosin staining. To assess inflamation and apoptosis immunohistochemically, espressions of markers such as TNF- α and Caspase-3 were examined and TAS and TOS were analyzed biochemically. Additionally, Nrf2/Keap1/HO-1 gene expressions were studied, along with measurements of ürea and creatinine levels. In this study, urografin administration led to a damage profile in kidney tissue characterized by increased TOS, decreased TAS and elevated TNF- α and Caspase-3 levels. Selenium treatment reversed these adverse changes, providind significant renal protection by activating the Nrf2/Keap1/HO-1 antiıxidant pathways and sppressing TNF- α and Caspase-3 expressions. In conclusion, selenium supplementation was found tobr effective in reducing urografin-induced renal injury and this effect was shown to occur through the reduction of oxidative stress and the enhancement of cellular defense mechanisms. Keywords: Nephropathy, NRF2/Keap1/HO-1, Oxidative Stress, Selenium, Urografin