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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 | Sensidvity to choli-nevgic drug treatments of aged rats with variable degrees of spatial memory impairment显示文摘 | Stemmelin J Cassel JC Will B | 1999 | Behav Brain Res1999，98，： | 1 |
| 3 | Factors affacting hydrocyclones perfor-mance显示文摘 | | 1980 | Mining Magazine1980，，2： | 1 |
| 4 | Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer显示文摘 | Berthelot J M Will B P Evans W K | 2000 | J Natl Cancer Inst2000，92，16： | 1 |
| 5 | Harnessing senescence delaying gases nitric oxide and nitrous oxide:a novel approach to postharvest control of fresh horticultural produce显示文摘 | Leshem Y Y Wills R B H | 1998 | Biologicat Plantacum1998，41，1： | 1 |
| 6 | Evidence for the function of the free radical gas - nitric oxide (NO) - as an endogenous maturation and senescence regulating factor in higher plants 显示文摘 | Leshem Y Y Wills R B H Ku V V V | 1998 | Plant Physiol Biochem1998，36，： | 1 |
| 7 | JAK2V617F-negative ET patients do not display constitutively active JAK/STAT signaling显示文摘 | Schwemmers S Will B Waller CF | 2007 | Exp Hematol2007，35，11： | 1 |
| 8 | A review on the morphology, molecular characterization, morphogenesis and pathogenesis of white spot syndrome virus显示文摘 | ESCOBEDO B C M ALDAY S V WILLE M | 2008 | Journal of Fish Diseases2008，31，1： | 1 |
| 9 | Accuracy of endoscopic ultra sonography in upper gastrointestinal submucosal lesions: a prospec- tive muhiccnter study 显示文摘 | Rosch T Kapfer B Will U | 2002 | Scand J Gastroenterol2002，37，7： | 1 |
| 10 | High Pressure Transformation of Cubic Boron Nitride from Amorphous Boron Nitride Using as Magnesium BoronNitride as the Catalyst显示文摘 | Singh B P Nover G Will G | 1995 | Journal of Crystal Growth1995，152，： | 1 |
| 11 | System identification of nonlinear state - space models 显示文摘 | T B Schon Adrian Wills Brett Ninness | 2011 | Automatica2011，47，： | 1 |
| 12 | On the Low-pressure Synthesis of Cubic Boron Nitride显示文摘 | B P Singh V L Solozhenko G Will | 1995 | Diamond and Related Materials1995，4，： | 1 |
| 13 | Hair removal policies in clean surgery: systematic review of randomized, controlled trials 显示文摘 | NIEL-WEISE B S WILLE J C VAN DEN BROEK P J | 2005 | Infec Control Hosp Epidemiol2005，26，12： | 1 |
| 14 | Humidifi- cation policies for mechanically ventilated intensive care patients and prevention of ventilator-associated pneumo- nia: a systematic review of randomized controlled trials 显示文摘 | Nil-Weise B S Wille J C van den Broek P J | 2007 | J Hosp Infect2007，65，4： | 1 |
| 15 | Optimization of storage conditions for shogur broccoli显示文摘 | Klieber A R Wills B H | | 0，，： | 1 |
| 16 | Diabetes mellitus and serum carutenoids: findings from the Third National Health and Nutrition Examination Survey显示文摘 | FORD E S WILL J C BOWMAN B A NARAYAN K M | 1999 | AM J Epidemiol1999，149，： | 1 |
| 17 | Distinguishing between anxiety, depression, and hostility: relations to anger-in, anger-out, and anger control 显示文摘 | Will B Bridewell Edward C Chang | 1997 | Personality Individual Difference1997，22，4： | 1 |
| 18 | Accuracy of endoscopic ultrasonography in upper gastrointestinal submucosal lesions:a prospective multicenter study显示文摘 | Rosch T Kapfer B Will U | 2002 | Scand J Gastroenterol2002，37，7： | 1 |
| 19 | Evidence for the function of the free radical gas-nitric oxide (NO)-as an endogenous maturation and senescence regulating factor in higher plants显示文摘 | Leshem Y Y Wills R B H Ku V V V | 1998 | Plant Physiol Biochem1998，36，11： | 1 |
| 20 | Recovery from brain injury in an- imals: relative efficacy of environmental enrichment, physical exercise or formal training ( 1990 - 2002) 显示文摘 | Will B Galani R Kelch C | 2004 | Prog Neurobiol2004，72，3： | 1 |
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