The effect of rosuvastatin on lung tissue in the sepsis model induced by cecal ligation and puncture in rats

Sepsis continues to be an important health problem due to its mortality rate of 30-90% despite modern treatments. Its pathogenesis includes the systemic inflammatory response to infection. It has been shown that statins have pleiotropic effects with their antioxidant, anti-inflammatory and immunomodulatory aspects independent of their cholesterol-lowering effects. Rosuvastatin has more enzyme-suppressing properties than other statins as well as higher pleiotrophic effects. Although a few studies showing the anti-inflammatory effect of rosuvastatin are available in the literature, its effect on sepsis has not been evaluated. In addition, there is no finding in the literature regarding the effect of rosuvastatin on apoptosis and autophagy induced as a result of tissue damage in sepsis. Our aim was to evaluate the effect of rosuvastatin against lung tissue damage in an experimental sepsis model induced by the cecal ligation and puncture (CLP) method. Six experimental groups were designed with Sprague-Dawley rats in each group: Sham, CLP, CLP+Rosuvastatin (10 mg/kg), CLP+Rosuvastatin (20 mg/kg), Sham+Rosuvastatin (10 mg/kg), Sham+Rosuvastatin (20 mg/kg). Rosuvastatin was administered concurrently orally, 5 hours before the surgical procedure. MDA and 8'OHdG were analyzed to determine the response to oxidative stress, and GSH was analyzed for its antioxidant property. The efficacy of rosuvastanin in the inflammation pathways of sepsis was evaluated immunohistochemically by NF-κβ/65 and caspas-3 expressions. Expressions of Bcl-2 and Bax genes for sepsis-induced apoptosis, and Beclin-1 and LC3 genes for autophagy were analyzed. Rosuvastatin had a protective effect on tissue damage caused by sepsis and the most effective dose was 10 mg/kg. However, its role in oxidative stress, inflammation, apoptosis and autophagy cellular pathways was supported by our findings. The therapeutic effect of a widely used drug such as rosuvastatin in sepsis, which has therapeutically challenging, complex and high mortality features, is an important finding. The findings of our study will shed light on the different potential effects of rosuvastatin and contribute to the formation of new treatment strategies.