PURPOSE: We determined whether anti-transforming growth factor-β (TGF-β) intervention could halt the progression of established radiation-induced liver fibrosis (RILF). METHODS AND MATERIALS: A replication-defective adenoviral vector expressing the extracellular portion of human TβRII and the Fc portion of immunoglobulin G fusion protein (AdTβRIIFc) was produced. The entire rat liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdTβRIIFc (1 × 10(11) plaque-forming units [PFU] of TβRII), control virus (1 × 10(11) PFU of AdGFP), or saline. Delayed radiation liver injury was assessed by histology and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell activation, and hepatocyte regeneration were also analyzed. RESULTS: In rats infected with AdTβRIIFc, fibrosis was significantly improved compared with rats treated with AdGFP or saline, as assessed by histology, hydroxyproline content, and serum level of hyaluronic acid. Compared with AdGFP rats, AdTβRIIFc-treated rats exhibited decreased oxidative stress damage and hepatic stellate cell activation and preserved liver function. CONCLUSIONS: Our results demonstrate that TGF-β plays a critical role in the progression of liver fibrosis and suggest that anti-TGF-β intervention is feasible and ameliorates established liver fibrosis. In addition, chronic oxidative stress may be involved in the progression of RILF.
PURPOSE: We determined whether anti-transforming growth factor-β (TGF-β) intervention could halt the progression of established radiation-induced liver fibrosis (RILF). METHODS AND MATERIALS: A replication-defective adenoviral vector expressing the extracellular portion of human TβRII and the Fc portion of immunoglobulin G fusion protein (AdTβRIIFc) was produced. The entire rat liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdTβRIIFc (1 × 10(11) plaque-forming units [PFU] of TβRII), control virus (1 × 10(11) PFU of AdGFP), or saline. Delayed radiation liver injury was assessed by histology and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell activation, and hepatocyte regeneration were also analyzed. RESULTS: In rats infected with AdTβRIIFc, fibrosis was significantly improved compared with rats treated with AdGFP or saline, as assessed by histology, hydroxyproline content, and serum level of hyaluronic acid. Compared with AdGFP rats, AdTβRIIFc-treated rats exhibited decreased oxidative stress damage and hepatic stellate cell activation and preserved liver function. CONCLUSIONS: Our results demonstrate that TGF-β plays a critical role in the progression of liver fibrosis and suggest that anti-TGF-β intervention is feasible and ameliorates established liver fibrosis. In addition, chronic oxidative stress may be involved in the progression of RILF.
Authors: Pei Zhang; Wanchang Cui; Kim G Hankey; Allison M Gibbs; Cassandra P Smith; Cheryl Taylor-Howell; Sean R Kearney; Thomas J MacVittie Journal: Health Phys Date: 2015-11 Impact factor: 1.316
Authors: Hamid A Bakshi; Mazhar S Al Zoubi; Faruck L Hakkim; Alaa A A Aljabali; Firas A Rabi; Amin A Hafiz; Khalid M Al-Batanyeh; Bahaa Al-Trad; Prawej Ansari; Mohamed M Nasef; Nitin B Charbe; Saurabh Satija; Meenu Mehta; Vijay Mishra; Gaurav Gupta; Salem Abobaker; Poonam Negi; Ibrahim M Azzouz; Ashref Ali K Dardouri; Harish Dureja; Parteek Prasher; Dinesh K Chellappan; Kamal Dua; Mateus Webba da Silva; Mohamed El Tanani; Paul A McCarron; Murtaza M Tambuwala Journal: Nutrients Date: 2020-06-26 Impact factor: 5.717