BACKGROUND: Previously, we clarified the role of inducible nitric oxide synthase (iNOS) and the protective effect of an iNOS inhibitor in warm ischemia and reperfusion model. In this study, we investigated whether the same effects would be obtained by iNOS inhibitor in liver transplantation model. MATERIAL AND METHODS: Orthotopic liver transplantation was performed in pigs in the usual manner after about 6 h of cold preservation in University of Wisconsin solution. Aminoguanidine hemisulfate (AG) was used as the iNOS inhibitor and AG was administered intraportally at the dose of 10 mg/kg just after reperfusion. Two experimental groups were subjected, control group (n = 10), and AG group (n = 10). We investigated changes of serum nitrite/nitrate (NOx) and aspartate aminotransferase (AST). Expression of iNOS was examined by immunohistochemistry, including a double immunofluorescnce technique in combination with cofocal laser scanning microscopy. RESULTS: Serum NOx and AST were significantly lower in the AG group. Histological hepatic damage and thrombocyte thrombi were attenuated in the AG group. Expression of iNOS was recognized strongly at Kupffer cells and neutrophils in the centrilobular region of liver after reperfusion by cofocal laser scanning microscopy. Moreover, iNOS staining was attenuated in AG group compared with control group. CONCLUSIONS: These results indicate that hepatic ischemia and reperfusion injury in liver transplantation might be triggered by iNOS expression of Kupffer cells and neutrophils, and attenuated by administration of an iNOS inhibitor. Moreover, AG showed down regulation of iNOS expression after reperfusion.
BACKGROUND: Previously, we clarified the role of inducible nitric oxide synthase (iNOS) and the protective effect of an iNOS inhibitor in warm ischemia and reperfusion model. In this study, we investigated whether the same effects would be obtained by iNOS inhibitor in liver transplantation model. MATERIAL AND METHODS: Orthotopic liver transplantation was performed in pigs in the usual manner after about 6 h of cold preservation in University of Wisconsin solution. Aminoguanidine hemisulfate (AG) was used as the iNOS inhibitor and AG was administered intraportally at the dose of 10 mg/kg just after reperfusion. Two experimental groups were subjected, control group (n = 10), and AG group (n = 10). We investigated changes of serum nitrite/nitrate (NOx) and aspartate aminotransferase (AST). Expression of iNOS was examined by immunohistochemistry, including a double immunofluorescnce technique in combination with cofocal laser scanning microscopy. RESULTS: Serum NOx and AST were significantly lower in the AG group. Histological hepatic damage and thrombocyte thrombi were attenuated in the AG group. Expression of iNOS was recognized strongly at Kupffer cells and neutrophils in the centrilobular region of liver after reperfusion by cofocal laser scanning microscopy. Moreover, iNOS staining was attenuated in AG group compared with control group. CONCLUSIONS: These results indicate that hepatic ischemia and reperfusion injury in liver transplantation might be triggered by iNOS expression of Kupffer cells and neutrophils, and attenuated by administration of an iNOS inhibitor. Moreover, AG showed down regulation of iNOS expression after reperfusion.
Authors: René Fahrner; Felix Dondorf; Michael Ardelt; Utz Settmacher; Falk Rauchfuss Journal: World J Gastroenterol Date: 2016-07-21 Impact factor: 5.742
Authors: Georgios Kyriakopoulos; Georgia Valsami; Christos Tsalikidis; Michail Pitiakoudis; Alexandra K Tsaroucha Journal: Ann Med Surg (Lond) Date: 2020-11-26
Authors: Wellington Andraus; Gabriela Freitas Pereira de Souza; Marcelo Ganzarolli de Oliveira; Luciana B P Haddad; Ana Maria M Coelho; Flavio Henrique Galvão; Regina Maria Cubero Leitão; Luiz Augusto Carneiro D'Albuquerque; Marcel Cerqueira Cesar Machado Journal: Clinics (Sao Paulo) Date: 2010-07 Impact factor: 2.365
Authors: Tomaz de Jesus Maria Grezzana Filho; Larisse Longo; Jorge Luiz Dos Santos; Gemerson Gabiatti; Carlos Boffil; Emanuel Bendo Dos Santos; Carlos Thadeu Schmidt Cerski; Marcio Fernandes Chedid; Carlos Otavio Corso Journal: Acta Cir Bras Date: 2020-05-08 Impact factor: 1.388