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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 | Molecular Fluorescence, Phosphorescence, and Chemiluminescence Spectrometry 显示文摘 | Oldham P B McCarroll M E McGown L B | 1993 | Anal Chem1993,72,12: | 2 |
| 3 | Mechanical properties of a biodegradable bone regeneration scaffold显示文摘 | Porter B D Oldham J B He S L | 2000 | J Biomech Eng2000,122,3: | 2 |
| 4 | Evaluation of a 2D diode array for IMRT quality assurance显示文摘 | Daniel Létourneau Misbah Gulam Di Yan Mark Oldham John W. Wong | 2003 | Radiotherapy and Oncology2003,,2: | 2 |
| 5 | Open butch urethropexy has a low rate of preoperative complications 显示文摘 | Kenton K Oldham L Brubaker L | 2002 | Obstet Gynecol2002,187,: | 1 |
| 6 | Open Burch urethropexy has a low rate of perioperative complications显示文摘 | Kenton K Oldham L Brubaker L | 2002 | Am J Obstet Gynecol2002,187,: | 1 |
| 7 | Superoxide dismutase as a target for the selective killing of cancer cells 显示文摘 | Huang P Feng L Oldham E | 2000 | Nature2000,407,: | 1 |
| 8 | Listen while you work? Quasi-experimental rela- tions between personal-stereo headset use and em- ployee work responses显示文摘 | Oldham G R Cummings A Mischel L J | 1995 | Journal of Applied Psy- chology1995,80,5: | 1 |
| 9 | Effects of supplementalVitamin A orβ-carotene during the dry period and early lactationon udder health显示文摘 | Oldham E R Eberhart R J Muller L D | 1991 | Journal of Dairy Science1991,74,11: | 1 |
| 10 | Double-cropping annual ryegrass and bermudagrass to reduce phosphorus levels in soil with history of poultry litter application显示文摘 | READ J J SISTANI K R OLDHAM J L | 2009 | Nutrient Cycling in Agroecosystems2009,,84: | 1 |
| 11 | Localisation of in- sulin- like growth factor receptors in skin follicles of sheep (Ovis aries) and changes during an induced growth cycle显示文摘 | NIXON A l FORD C A OLDHAM J M | 1997 | Comp Bio- chem Physiol A Physiol1997,118,4: | 1 |
| 12 | Effect of testosterone on binding of insulin-like growth factor- I ( IGF- I ) and IGF- 1I in growing antlers of fallow deer ( Dama dama) 显示文摘 | Elloitt J L Oldham J M Asher G W et at | 1996 | Growth Regul1996,6,4: | 1 |
| 13 | Cell mediated immunity to liver antigens during experimental Fasciola hepatica infection of cattle显示文摘 | Oldham G Williams L | 1985 | Parasite Immunol1985,7,: | 1 |
| 14 | Survey of symptoals, respiratory function,and immunology and their relation to glutaraldehyde and other occupational exposures among endoscope nursing Employee显示文摘 | Vyas A Pickering C Oldham L | 2000 | Oeeup Environ Meal2000,57,7: | 1 |
| 15 | Electroosmotically transported baseline perturbations in capillary electrophoresis显示文摘 | Colyer C L Oldham K B Sokirko A V | 1995 | Anal Chem1995,67,18: | 1 |
| 16 | Cone-beam-Ct guided radiation therapy A model for on-line application显示文摘 | Oldham M Letourneau D Watt L | 2005 | Ra diother Oncol2005,75,3: | 1 |
| 17 | Open butch urethfopexy has a low rate of perioperative complications显示文摘 | Kenton K Oldham L Brubaker L | 2002 | Obstet Gynecol2002,187,4: | 1 |
| 18 | Implicit and explicit control of motor actions: Revisiting some early evidence显示文摘 | MULLEN R HARDY L OLDHAM A | 2007 | British J Psychol2007,98,1: | 1 |
| 19 | Toxico- logical considerations on the use of propylene glycol as a hu mectant in cigarettes显示文摘 | Gaworski C L Oldham M J Coggins C R | 2010 | Toxicology2010,269,1: | 1 |
| 20 | Crystal structure of the severe acute respiratory syndrome(SARS)coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between corona-and arteriviridae显示文摘 | YU I M OLDHAM M L ZHANG J | 2006 | J Biol Chem2006,281,17: | 1 |