N-acetylcysteine prevents carbon tetrachloride-induced liver cirrhosis: role of liver transforming growth factor-beta and oxidative stress

2009 ◽  
Vol 21 (8) ◽  
pp. 908-914 ◽  
Author(s):  
Marina Galicia-Moreno ◽  
Adriana Rodríguez-Rivera ◽  
Karina Reyes-Gordillo ◽  
José Segovia ◽  
Mineko Shibayama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Cirrhosis ◽  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta ◽  
And Oxidative Stress

scholarly journals The TGFβ1 Receptor Antagonist GW788388 Reduces JNK Activation and Protects Against Acetaminophen Hepatotoxicity in Mice

2019 ◽  
Vol 170 (2) ◽  
pp. 549-561 ◽  
Author(s):  
Matthew McMillin ◽  
Stephanie Grant ◽  
Gabriel Frampton ◽  
Anca D Petrescu ◽  
Elaina Williams ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Growth Factor ◽  
Liver Injury ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Growth Factor Beta ◽  
And Oxidative Stress

Abstract Acute liver failure is a serious consequence of acetaminophen (APAP)-induced hepatotoxic liver injury with high rates of morbidity and mortality. Transforming growth factor beta 1 (TGFβ1) is elevated during liver injury and influences hepatocyte senescence during APAP-induced hepatotoxicity. This study investigated TGFβ1 signaling in the context of inflammation, necrotic cell death, and oxidative stress during APAP-induced liver injury. Male C57Bl/6 mice were injected with 600 mg/kg APAP to generate liver injury in the presence or absence of the TGFβ receptor 1 inhibitor, GW788388, 1 h prior to APAP administration. Acetaminophen-induced liver injury was characterized using histological and biochemical measures. Transforming growth factor beta 1 expression and signal transduction were assessed using immunohistochemistry, Western blotting and ELISA assays. Hepatic necrosis, liver injury, cell proliferation, hepatic inflammation, and oxidative stress were assessed in all mice. Acetaminophen administration significantly induced necrosis and elevated serum transaminases compared with control mice. Transforming growth factor beta 1 staining was observed in and around areas of necrosis with phosphorylation of SMAD3 observed in hepatocytes neighboring necrotic areas in APAP-treated mice. Pretreatment with GW788388 prior to APAP administration in mice reduced hepatocyte cell death and stimulated regeneration. Phosphorylation of SMAD3 was reduced in APAP mice pretreated with GW788388 and this correlated with reduced hepatic cytokine production and oxidative stress. These results support that TGFβ1 signaling plays a significant role in APAP-induced liver injury by influencing necrotic cell death, inflammation, oxidative stress, and hepatocyte regeneration. In conclusion, targeting TGFβ1 or downstream signaling may be a possible therapeutic target for the management of APAP-induced liver injury.

scholarly journals Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Jelena Krstić ◽  
Drenka Trivanović ◽  
Slavko Mojsilović ◽  
Juan F. Santibanez
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Careful Consideration ◽  
Cancer Therapies ◽  
Antitumor Effects ◽  
Growth Factor Beta ◽  
And Oxidative Stress

Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-βand ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-βcan control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-βsignaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-βand ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation but also may collaborate in cancer progression. The mutual collaboration of TGF-βand ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies.

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