BACKGROUND/AIMS: Increased intrahepatic resistance (IHR) in cirrhosis is due to fibrosis and hepatic endothelial dysfunction (HED). Besides producing fibrosis, increased reactive oxygen species (ROS) promotes ROS-related nitration of anti-oxidative enzymes in cirrhotic livers. Tyrosine nitration (nitrotyrosilation)-related inactivation of anti-oxidative enzymes is increased in cirrhotic livers. This study investigates effects of N-acetylcysteine (NAC) administrations in bile-duct-ligation (BDL) rats. METHODS: This study measured portal venous pressure (PVP), IHR, hepatic endothelial function, hepatic levels of anti-oxidants and oxidants, type III procollagen (PIIIP), proteins expression of thromboxane synthase (TXS), nitrotyrosine, manganese superoxide dismutase (MnSOD), and hepatic NOx and thromboxane A(2) (TXA(2)) production in perfusates. RESULTS: The improvement of HED was associated with decreased PVP and IHR, hepatic protein and mRNA levels of PIIIP, protein expression of TXS and nitrotyrosine, oxidants and production of TXA(2) in NAC-treated BDL rat livers. Conversely, hepatic NOx production, anti-oxidants, and protein expression of MnSOD were increased in NAC-treated BDL rat livers. CONCLUSIONS: In NAC-treated cirrhotic rats, the decrease in IHR was mainly caused by its anti-oxidative effect-related prevention of hepatic fibrogenesis associated with the decrease of oxidants-related nitrotyrosilation and improvement of HED.
BACKGROUND/AIMS: Increased intrahepatic resistance (IHR) in cirrhosis is due to fibrosis and hepatic endothelial dysfunction (HED). Besides producing fibrosis, increased reactive oxygen species (ROS) promotes ROS-related nitration of anti-oxidative enzymes in cirrhotic livers. Tyrosine nitration (nitrotyrosilation)-related inactivation of anti-oxidative enzymes is increased in cirrhotic livers. This study investigates effects of N-acetylcysteine (NAC) administrations in bile-duct-ligation (BDL) rats. METHODS: This study measured portal venous pressure (PVP), IHR, hepatic endothelial function, hepatic levels of anti-oxidants and oxidants, type III procollagen (PIIIP), proteins expression of thromboxane synthase (TXS), nitrotyrosine, manganese superoxide dismutase (MnSOD), and hepatic NOx and thromboxane A(2) (TXA(2)) production in perfusates. RESULTS: The improvement of HED was associated with decreased PVP and IHR, hepatic protein and mRNA levels of PIIIP, protein expression of TXS and nitrotyrosine, oxidants and production of TXA(2) in NAC-treated BDL rat livers. Conversely, hepatic NOx production, anti-oxidants, and protein expression of MnSOD were increased in NAC-treated BDL rat livers. CONCLUSIONS: In NAC-treated cirrhotic rats, the decrease in IHR was mainly caused by its anti-oxidative effect-related prevention of hepatic fibrogenesis associated with the decrease of oxidants-related nitrotyrosilation and improvement of HED.
Authors: André de Lima Aires; Mônica Camelo Pessôa de Azevedo Albuquerque; Renata Alexandre Ramos Silva; Giuliana Viegas Schirato; Nicodemos Teles de Pontes Filho; Sidcley Bernardino de Araújo; Valdênia Maria Oliveira Souza; Vlaudia Maria Assis Costa; Elizabeth Malagueño Journal: Parasitol Res Date: 2012-07-07 Impact factor: 2.289
Authors: Colin T Shearn; Blair Fennimore; David J Orlicky; Yue R Gao; Laura M Saba; Kayla D Battista; Stefanos Aivazidis; Mohammed Assiri; Peter S Harris; Cole Michel; Gary F Merrill; Edward E Schmidt; Sean P Colgan; Dennis R Petersen Journal: Free Radic Biol Med Date: 2019-08-01 Impact factor: 7.376
Authors: Rafael Vercelino; Irene Crespo; Gabriela F P de Souza; Maria Jose Cuevas; Marcelo G de Oliveira; Norma Possa Marroni; Javier González-Gallego; María Jesús Tuñón Journal: J Mol Med (Berl) Date: 2010-01-09 Impact factor: 4.599