This study is aimed to investigate whether simvastatin induces cardiomyocytes survival signaling in endotoxin (lipopolysaccharide, LSP)-induced myocardial injury, and if so, further to determine a role of survivin in simvastatin-anti-apoptotic effect. Wistar rats were pretreated with simvastatin (10-40 mg/kg po) before a single non-lethal dose of LPS. In myocardial tissue, LPS induced structural disorganization of myofibrils with significant inflammatory infiltrate (cardiac damage score, CDS = 3.87 ± 0.51, p < 0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS (p < 0.01). Simvastatin in 20 mg/kg and 40 mg/kg pretreatment, dose dependently, attenuated myocardial apoptosis determined as apoptotic index (28.8 ± 4.5% and 18.9 ± 3.5, p < 0.05), decreased cleaved caspase-3 expression (32.1 ± 5.8%, p < 0.01), along with significant Bcl-xL expression in the simvastatin groups (p < 0.01). Interestingly, in the simvastatin groups were determined significantly increased expression of survivin (p < 0.01), but in negative correlation with cleaved caspase-3 and apoptotic indices (p < 0.01). Simvastatin has a cardioprotective effects against LPS induced apoptosis. The effect may be mediated by up-regulation of survivin via activation of NF-κB, which leads to reduced activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis.

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanského 62 500 03 Hradec Králové Czech Republic

Department of Pharmacology Toxicology and Clinical Pharmacology School of Medicine University of Banja Luka 14 Save Mrkalja St 78000 Banja Luka Bosnia and Herzegovina

Institute of Pathology University Clinical Center of Republic of Srpska School of Medicine University of Banja Luka 12 Beba St 78000 Banja Luka Bosnia and Herzegovina

Medical Faculty of the Military Medical Academy University of Defense in Belgrade 1 Pavla Jurišića Šturma St 11000 Belgrade Serbia

National Poison Control Centre Military Medical Academy 11 Crnotravska St 11000 Belgrade Serbia

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