BACKGROUND: The protective role of heme oxygenase-1 (HO-1) against liver ischemia-reperfusion (I/R) injury in models of hypoxic and remote preconditioning has been proved. The feasible candidates who induce HO-1 and thorough which exert the protective effects are under investigation. The aim was to study the role of HO-1 in pharmacological preconditioning by simvastatin in a rat model. METHODS: Pharmacological preconditioning by intraperitoneal injection of simvastatin (5 mg/kg) was tested on a partial liver I/R model on rats. The expression of HO-1 protein and enzyme activities in livers, serum alanine transaminase (ALT) levels, and TUNEL staining of liver after I/R injury were measured in rats with and without simvastatin preconditioning. RESULTS: HO-1 was induced and persistently overexpressed in the hepatocytes 24 hr after simvastatin treatment. Simvastatin preconditioning diminished the elevation of serum ALT levels 4 hr after I/R injury (69.6+/-26.3 U/L) (P<0.05 vs. other groups) when compared with control (403.8+/-261.9 U/L) and zinc protoporphyrin (ZnPP)-pretreated (717.5+/-205.6 U/L) groups. Simvastatin preconditioning diminished the apoptosis after I/R injury as well (apoptosis index: 26.4+/-8 for Simvastatin, 78+/-7 for control, and 85.3+/-2 for ZnPP group; P<0.05). The addition of ZnPP negated the protective effects of simvastatin as evidenced in the ALT level (406.2+/-243.0 U/L) and apoptosis index (75.6+/-6). The heme oxygenase activity in treated rats correlated with these results. CONCLUSIONS: The induction of HO-1 by simvastatin preconditioning played a protective role against hepatic I/R injury.
BACKGROUND: The protective role of heme oxygenase-1 (HO-1) against liver ischemia-reperfusion (I/R) injury in models of hypoxic and remote preconditioning has been proved. The feasible candidates who induce HO-1 and thorough which exert the protective effects are under investigation. The aim was to study the role of HO-1 in pharmacological preconditioning by simvastatin in a rat model. METHODS: Pharmacological preconditioning by intraperitoneal injection of simvastatin (5 mg/kg) was tested on a partial liver I/R model on rats. The expression of HO-1 protein and enzyme activities in livers, serum alanine transaminase (ALT) levels, and TUNEL staining of liver after I/R injury were measured in rats with and without simvastatin preconditioning. RESULTS:HO-1 was induced and persistently overexpressed in the hepatocytes 24 hr after simvastatin treatment. Simvastatin preconditioning diminished the elevation of serum ALT levels 4 hr after I/R injury (69.6+/-26.3 U/L) (P<0.05 vs. other groups) when compared with control (403.8+/-261.9 U/L) and zinc protoporphyrin (ZnPP)-pretreated (717.5+/-205.6 U/L) groups. Simvastatin preconditioning diminished the apoptosis after I/R injury as well (apoptosis index: 26.4+/-8 for Simvastatin, 78+/-7 for control, and 85.3+/-2 for ZnPP group; P<0.05). The addition of ZnPP negated the protective effects of simvastatin as evidenced in the ALT level (406.2+/-243.0 U/L) and apoptosis index (75.6+/-6). The heme oxygenase activity in treated rats correlated with these results. CONCLUSIONS: The induction of HO-1 by simvastatin preconditioning played a protective role against hepatic I/R injury.
Authors: Mohamed Bejaoui; Eirini Pantazi; Emma Folch-Puy; Pedro M Baptista; Agustín García-Gil; René Adam; Joan Roselló-Catafau Journal: World J Gastroenterol Date: 2015-01-14 Impact factor: 5.742
Authors: Mohammed Reza Moussavian; Claudia Scheuer; Michael Schmidt; Otto Kollmar; Matthias Wagner; Maximilian von Heesen; Martin K Schilling; Michael D Menger Journal: Langenbecks Arch Surg Date: 2010-06-27 Impact factor: 3.445
Authors: Nadav Slijper; Igor Sukhotnik; Elena Chemodanov; Yulia Bashenko; Ron Shaoul; Arnold G Coran; Jorge Mogilner Journal: Pediatr Surg Int Date: 2010-01 Impact factor: 1.827