Abstract / Summary
Various intracellular signaling mechanisms are involved in lung ischemia and subsequent tissue damage resulting from reperfusion. Inflammation and oxidative stress play significant roles in the pathophysiology. However, there is not enough literature on the importance of necroptosis in lung ischemia-reperfusion (IR) injury. Dexpanthenol (DEX), a derivative of vitamin B5 used in the study, attracts attention with its potential tissue-protective effects. The present study aimed to evaluate the protective effects of DEX on pulmonary injury induced by IR and to elucidate its potential mechanisms of action, particularly its anti-inflammatory, anti-necrotic, and antioxidant properties. Forty male Wistar rats were randomly divided into four groups, each consisting of 10 rats: Sham, IR, IR-DEX, and DEX. Rats were treated with a single dose of 500 mg/kg DEX intraperitoneally 30 min before thoracotomy. Then, animals that applied ischemia in IR and IR-DEX groups were exposed to hilus clamping for 60 min, and 60 min reperfusion was performed in the relevant reperfusion groups. After sacrification, tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analysis. IR injury resulted in significant increases in tumor necrosis factor-α, caspase-3 activity, necroptosis-related markers, and oxidative stress parameters. Histopathological examination revealed pronounced alveolar damage, marked hyperemia, and increased septal thickness. Furthermore, biochemical indicators of oxidative stress, including total oxidant status and oxidative stress index, as well as molecular markers evaluated in this study—vascular endothelial growth factor and receptor-interacting serine/threonine-protein kinases 1 and 3 —were elevated following IR injury, whereas total antioxidant status levels were reduced. In contrast, the IR + DEX group demonstrated marked improvement across all evaluated biochemical, molecular, and histopathological parameters. DEX used in this study is a promising drug that can be used to reduce and treat IR-induced lung injury by preventing several intracellular pathways, including necroptosis, apoptosis, and inflammation.