Akiko Eguchi1, Toru Yoshitomi2, Milos Lazic1, Casey D Johnson1, Long Binh Vong2, Alexander Wree1, Davide Povero1, Bettina G Papouchado3, Yukio Nagasaki2,4,5, Ariel E Feldstein1. 1. Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA. 2. Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. 3. Department of Pathology, VA San Diego Healthcare System, San Diego, CA 92161, USA. 4. Master's School of Medical Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. 5. Satellite Laboratory of International Center for Materials Nanoarchitechtonics (WPI-MANA), National Institute of Materials Science (NIMS), Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
Abstract
AIM: Oxidative stress (OS) is largely thought to be a central mechanism responsible for liver damage, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Our aim was to investigate whether suppression of OS in the liver via redox nanoparticles (RNPs) reduces liver damage in a mouse model of NASH. MATERIALS & METHODS: RNPs were prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals and were orally administered by daily gavage for 4 weeks. RESULTS: The redox polymer was delivered to the liver after disintegration of nanoparticle in the stomach. RNP treatment in NASH mice via gavage led to a reduction of liver OS, improvement of fibrosis, and significant reduction of inflammation. CONCLUSION: These findings uncover RNP as a novel potential NASH therapy.
AIM: Oxidative stress (OS) is largely thought to be a central mechanism responsible for liver damage, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Our aim was to investigate whether suppression of OS in the liver via redox nanoparticles (RNPs) reduces liver damage in a mouse model of NASH. MATERIALS & METHODS: RNPs were prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals and were orally administered by daily gavage for 4 weeks. RESULTS: The redox polymer was delivered to the liver after disintegration of nanoparticle in the stomach. RNP treatment in NASH mice via gavage led to a reduction of liver OS, improvement of fibrosis, and significant reduction of inflammation. CONCLUSION: These findings uncover RNP as a novel potential NASH therapy.
Authors: Alexander Wree; Matthew D McGeough; Carla A Peña; Martin Schlattjan; Hongying Li; Maria Eugenia Inzaugarat; Karen Messer; Ali Canbay; Hal M Hoffman; Ariel E Feldstein Journal: J Mol Med (Berl) Date: 2014-05-28 Impact factor: 4.599
Authors: Alexander Wree; Lori Broderick; Ali Canbay; Hal M Hoffman; Ariel E Feldstein Journal: Nat Rev Gastroenterol Hepatol Date: 2013-08-20 Impact factor: 46.802
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: B C Yuksel; S E Serdar; A Tuncel; N Uzum; O Ataoglu; A Atan; S Hengirmen; A B Iskit; M O Guc Journal: Eur Surg Res Date: 2009-06-25 Impact factor: 1.745