scholarly journals Double Knockout of Peroxiredoxin 4 (Prdx4) and Superoxide Dismutase 1 (Sod1) in Mice Results in Severe Liver Failure

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Takujiro Homma ◽  
Toshihiro Kurahashi ◽  
Jaeyong Lee ◽  
Atsunori Nabeshima ◽  
Sohsuke Yamada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Liver Failure ◽  
Liver Steatosis ◽  
Superoxide Dismutase 1 ◽  
Severe Liver ◽  
Double Knockout ◽  
Nonalcoholic Fatty Liver ◽  
Triglyceride Rich Lipoprotein ◽  
Young Stage

Mice that are deficient in superoxide dismutase 1 (Sod1), an antioxidative enzyme, are susceptible to developing liver steatosis. Peroxiredoxin 4 (Prdx4) catalyzes disulfide bond formation in proteins via the action of hydrogen peroxide and hence decreases oxidative stress and supports oxidative protein folding for the secretion of lipoproteins. Because elevated reactive oxygen species induce endoplasmic reticulum stress, this negative chain reaction is likely involved in the development of nonalcoholic fatty liver diseases and more advanced steatohepatitis (NASH). In the current study, we generated Prdx4 and Sod1 double knockout (DKO; Prdx4−/ySod1−/−) mice and examined whether the combined deletion of Prdx4 and Sod1 aggravated liver pathology compared to single knockout and wild-type mice. The secretion of triglyceride-rich lipoprotein was strikingly impaired in the DKO mice, leading to aggravated liver steatosis. Simultaneously, the activation of caspase-3 in the liver was observed. The hyperoxidation of Prdxs, a hallmark of oxidative stress, occurred in different isoforms that are uniquely associated with Sod1−/− and Prdx4−/y mice, and the effect was additive in DKO mouse livers. Because DKO mice spontaneously develop severe liver failure at a relatively young stage, they have the potential for use as a model for hepatic disorders and for testing other potential treatments.

scholarly journals Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

FEBS Open Bio ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 522-532 ◽  
Author(s):  
Yoshitaka Kondo ◽  
Hirofumi Masutomi ◽  
Yoshihiro Noda ◽  
Yusuke Ozawa ◽  
Keita Takahashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Hepatic Steatosis ◽  
Knockout Mice ◽  
Superoxide Dismutase 1 ◽  
Marker Protein ◽  
Double Knockout

Aging and oxidative stress alter DNA repair mechanisms in male germ cells of superoxide dismutase-1 null mice

2021 ◽  
Author(s):  
Paulina Nguyen-Powanda ◽  
Bernard Robaire
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Superoxide Dismutase ◽  
Germ Cells ◽  
Superoxide Dismutase 1 ◽  
Male Germ Cells ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
And Oxidative Stress

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.

scholarly journals Role of mitophagy regulation by ROS in hepatic stellate cells during acute liver failure

2018 ◽  
Vol 315 (3) ◽  
pp. G374-G384 ◽  
Author(s):  
Zhen Tian ◽  
Yi Chen ◽  
Naijuan Yao ◽  
Chunhua Hu ◽  
Yuchao Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Oxygen Species ◽  
End Stage Liver Disease ◽  
End Stage

Liver sinusoids serve as the first line of defense against extrahepatic stimuli from the intestinal tract. Hepatic stellate cells (HSCs) are pericytes residing in the perisinusoidal space that integrate cytokine-mediated inflammatory responses in the sinusoids and relay these signals to the liver parenchyma. Oxidative stress has been shown to promote inflammation during acute liver failure (ALF). Whether and how oxidative stress is involved in HSC inflammation during ALF remains unclear. Level of systemic oxidative stress is reflected by superoxide dismutase (SOD). Thus, ALF patients were recruited to investigate the correlation between plasma SOD levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation. SOD2 expression and HSCs activation were investigated by immunohistochemistry. Inflammation, mitophagy, and apoptosis were investigated by immunoblot analysis and flow cytometry in HSCs treated with lipopolysaccharide (LPS) and reactive oxygen species (ROS) donors. The plasma SOD level was significantly increased in patients with ALF compared with those with cirrhosis (444.4 ± 23.58 vs. 170.07 ± 3.52 U/ml, P < 0.01) and was positively correlated with the Model for End-Stage Liver Disease-Na score ( R2 = 0.4720, P < 0.01). In vivo observations revealed that SOD2 immunostaining was increased in ALF patients and mice models, and in vitro experiments demonstrated that LPS/ROS promoted inflammation via inhibiting mitophagy. Moreover, the regulation of inflammation was apoptosis independent in HSCs. LPS-induced increases in oxidative stress promote inflammation through inhibiting mitophagy in HSCs during the process of ALF, providing a novel strategy for the treatment of patients with ALF. NEW & NOTEWORTHY Here we demonstrate that the serum superoxide dismutase (SOD) level is significantly increased in patients with acute liver failure (ALF), and, correlated with the Model for End-Stage Liver Disease-Na score, SOD level dropped in the remission stage of ALF. We identify that, in liver tissue from ALF patients and mice models, manganese-dependent SOD was overexpressed, and show lipopolysaccharide/H2O2 inhibits mitophagy via reactive oxygen species in hepatic stellate cells (HSCs). We show that inhibited mitophagy promotes inflammation in HSCs, whereas mitophagy inducer rescues HSCs from lipopolysaccharide-induced inflammation.

Severe liver steatosis correlates with nitrosative and oxidative stress in rats

2008 ◽  
Vol 38 (7) ◽  
pp. 523-530 ◽  
Author(s):  
I. Grattagliano ◽  
P. Caraceni ◽  
G. Calamita ◽  
D. Ferri ◽  
I. Gargano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Steatosis ◽  
Severe Liver ◽  
And Oxidative Stress

Effects of Oxidative Stress on the Conjunctiva in Cu, Zn-Superoxide Dismutase-1 (Sod1)–Knockout Mice

2015 ◽  
Vol 56 (13) ◽  
pp. 8382 ◽  
Author(s):  
Takashi Kojima ◽  
Murat Dogru ◽  
Osama M. A. Ibrahim ◽  
Tais Hitomi Wakamatsu ◽  
Masataka Ito ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Knockout Mice ◽  
Superoxide Dismutase 1

scholarly journals Attenuation of High-Fat Diet-Induced Rat Liver Oxidative Stress and Steatosis by Combined Hydroxytyrosol- (HT-) Eicosapentaenoic Acid Supplementation Mainly Relies on HT

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Francisca Echeverría ◽  
Rodrigo Valenzuela ◽  
Andrés Bustamante ◽  
Daniela Álvarez ◽  
Macarena Ortiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Eicosapentaenoic Acid ◽  
High Fat Diet ◽  
Control Diet ◽  
Liver Steatosis ◽  
Pharmacological Therapy ◽  
High Fat ◽  
Total Recovery ◽  
Nonalcoholic Fatty Liver ◽  
The Impact

Pharmacological therapy for nonalcoholic fatty liver disease (NAFLD) is not approved at the present time. For this purpose, the effect of combined eicosapentaenoic acid (EPA; 50 mg/kg/day) modulating hepatic lipid metabolism and hydroxytyrosol (HT; 5 mg/kg/day) exerting antioxidant actions was evaluated on hepatic steatosis and oxidative stress induced by a high-fat diet (HFD; 60% fat, 20% protein, and 20% carbohydrates) compared to a control diet (CD; 10% fat, 20% protein, and 70% carbohydrates) in mice fed for 12 weeks. HFD-induced liver steatosis (i) was reduced by 32% by EPA, without changes in oxidative stress-related parameters and mild recovery of Nrf2 functioning affording antioxidation and (ii) was decreased by 42% by HT, concomitantly with total regain of the glutathione status diminished by HFD, 42% to 59% recovery of lipid peroxidation and protein oxidation enhanced by HFD, and regain of Nrf2 functioning, whereas (iii) combined EPA + HT supplementation elicited 74% reduction in liver steatosis, with total recovery of the antioxidant potential in a similar manner than HT. It is concluded that combined HT + EPA drastically decreases NAFLD development, an effect that shows additivity in HT and EPA effects that mainly relies on HT, strengthening the impact of oxidative stress as a central mechanism underlying liver steatosis in obesity.

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