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| 1 | Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction显示文摘AIM To comprehensively evaluate mitochondrial(dys) function in preclinical models of nonalcoholic steatohepatitis(NASH).METHODS We utilized two readily available mouse models of nonalcoholic fatty liver disease(NAFLD) with or without progressive fibrosis: Lep^(ob)/Lep^(ob)(ob/ob) and FATZO mice on high trans-fat, high fructose and high cholesterol(AMLN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling. Morphological features of mitochondria were assessed via transmission electron microscopy and immunofluorescence, and function was assessed by measuring oxidative capacity in primary hepatocytes, and respiratory control and proton leak in isolated mitochondria. Oxidative stress was measured by assessing activity and/or expression levels of Nrf1, Sod1, Sod2, catalase and 8-OHdG. RESULTS When challenged with AMLN diet for 12 wk, ob/ob and FATZO mice developed steatohepatitis in the presence of obesity and hyperinsulinemia. NASH development was associated with hepatic mitochondrial abnormalities, similar to those previously observed in humans, including mitochondrial accumulation and increased proton leak. AMLN diet also resulted in increased numbers of fragmented mitochondria in both strains of mice. Despite similar mitochondrial phenotypes, we found that ob/ob mice developed more advanced hepatic fibrosis. Activity of superoxide dismutase(SOD) was increased in ob/ob AMLN mice, whereas FATZO mice displayed increased catalase activity, irrespective of diet. Furthermore, 8-OHd G, a marker of oxidative DNA damage, was significantly increased in ob/ob AMLN mice compared to FATZO AMLN mice. Therefore, antioxidant capacity reflected as the ratio of catalase:SOD activity was similar between FATZO and C57 BL6 J control mice, but significantly perturbed in ob/ob mice. CONCLUSION Oxidative stress, and/or the capacity to compensate for increased oxidative stress, in the setting of mitochondrial dysfunction, is a key factor for development of hepatic injury and fibrosis in these mouse models. | Michelle L Boland Stephanie Oldham Brandon B Boland Sarah Will Jean-Martin Lapointe Silvia Guionaud Christopher J Rhodes James L Trevaskis | 2018 | World Journal of Gastroenterology2018，24，16： | 7 |
| 2 | DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate显示文摘 | Mary Premenko-Lanier Paul A Rota Gary Rhodes David Verhoeven Dan H Barouch Nicholas W Lerche Norman L Letvin William J Bellini Michael B McChesney | 2003 | Virology2003，，1： | 2 |
| 3 | Genes affecting foliage color in watermelon显示文摘 | RHODES B B | 1986 | J Hered1986，77，： | 1 |
| 4 | Prevalence of arrhythmias during exercise stress testing in patients with congenital heart disease and severe right ventricular con- duit dysfunction显示文摘 | Priromprintr B Rhodes J Silka MJ | 2014 | Am J Cardiol2014，114，3： | 1 |
| 5 | Optimal linear image combination显示文摘 | Rowe B Hirata C Rhodes J | 2011 | The Astronomical Journal2011，74，： | 1 |
| 6 | Analysis of a single nucleotide polymorphism that controls the cooking quality of rice using a non-gel based assay 显示文摘 | Bormans C A Rhodes R B Kephart D D | 2002 | Euphytica2002，128，： | 1 |
| 7 | Impact of air staging on the fate of NO and N2O in a circulating fluidized-bed combustor 显示文摘 | Wang X S Gibbs B M Rhodes M J | 1994 | Combustion and Flame1994，99，34： | 1 |
| 8 | Performance of large-aperture optical:switches for high energy inertial-confinement fusion lasers显示文摘 | Mark A Rhodes B Woods J J DeYoreo | 1995 | Applied Optics1995，34，53： | 1 |
| 9 | Internal spatial modes in glass microring resonators显示文摘 | Goldberg B B Unlu M S Chu S T Little B | 2000 | IEEE Journal on Selected Topics in Quantum Electronics2000，，： | 1 |
| 10 | RAPD molecular marker in watermelon显示文摘 | Zhang X P Rhodes B B | 1993 | Hortscience1993，28，5： | 1 |
| 11 | Regulation of the follicle-stimulating hormone beta gene by the LHX3 LIM-homeodomain transcription factor显示文摘 | West B E Parker G E Savage J J Kiratipranon P Toomey K S Beach L R Colvin S C Sloop KW Rhodes S J | | 0，，： | 1 |
| 12 | Septic arthritis in children显示文摘 | MORREY B F BIANCO A J Jr RHODES K H | 1975 | Orthop Clin Noah Am1975，6，4： | 1 |
| 13 | Evaluation of HER-2/neu immunohistochemical assay sensitivity and scoring on formalin-fixed and paraffin-processed cell lines and breast tumors:a comparative study involving results from laboratories in 21 countries显示文摘 | JASANI B ANDERSON E | 2002 | Am J Clin Pathol2002，118，3： | 1 |
| 14 | Single gene control of anthracnose resistance in Citrullus? 显示文摘 | Love S L Rhodes B B | 1988 | cucurbit genetics cooperative report1988，11，： | 1 |
| 15 | Prediction of plant microRNA targets 显示文摘 | Rhodes M W Reinhart B J | 2002 | Cell2002，110，： | 1 |
| 16 | Albumin micrespheres for study of the reticuloendothial system显示文摘 | Scheffel U Rhodes B A Natarazan T K | 1973 | J Nucl Med1973，13，： | 1 |
| 17 | Pathology of neonatal calf diarrhea induced by a coronavirus-like agent显示文摘 | Mebus C A Stair E L Rhodes M B | 1973 | Vet Pathol1973，10，： | 1 |
| 18 | A test of the theory of reference-dependent preferences 显示文摘 | Bateman I Munro A Rhodes B etal | 1997 | Quarterly Journal of Economics1997，112，2： | 1 |
| 19 | Corrosion behavior of friction stir welded AA7050- T7651 显示文摘 | LUMSDEN J B MAHONEY M W RHODES C G POLLOCK G A | 2003 | Corrosion2003，59，3： | 1 |
| 20 | The low-temperature hydrolysis of carbonyl sulfide and carbon disulfide:A review显示文摘 | RHODES C RIDDEL S A WEST J PETER WILLIAMS B HUTCHINGS G J | 2000 | Catal Today2000，59，34： | 1 |
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