Apocynin administration prevents the changes induced by a fructose-rich diet on rat liver metabolism and the antioxidant system

2012 ◽  
Vol 123 (12) ◽  
pp. 681-692 ◽  
Author(s):  
María Cecilia Castro ◽  
Flavio Francini ◽  
Guillermo Schinella ◽  
Claudia Inés Caldiz ◽  
María Guillermina Zubiría ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drinking Water ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Oxidase Activity ◽  
Fatty Acid Synthase ◽  
Control Diet ◽  
Liver Steatosis ◽  
Nadph Oxidase Activity ◽  
Gene And Protein Expression

In the present study, we investigated the role of NADPH oxidase in F (fructose)-rich-diet-induced hepatic OS (oxidative stress) and metabolic changes, and their prevention by apocynin co-administration. Wistar rats were fed for 21 days on (i) a control diet, (ii) a control diet plus 10% F in the drinking water, (iii) a control diet with apocynin in the drinking water (CA) and (iv) F plus apocynin in the drinking water (FA). Glycaemia, triglyceridaemia, NEFAs (non-esterified fatty acids) and insulinaemia were determined. In the liver, we measured (i) NADPH oxidase activity, and gene and protein expression; (ii) protein carbonyl groups, GSH and TBARSs (thiobarbituric acid-reactive substances); (iii) catalase, CuZn-SOD (superoxide dismutase) and Mn-SOD expression; (iv) liver glycogen and lipid content; (v) GK (glucokinase), G6Pase (glucose-6-phosphatase) and G6PDH (glucose-6-phosphate dehydrogenase) activities; (vi) FAS (fatty acid synthase), GPAT (glycerol-3-phosphate acyltransferase), G6Pase and G6PDH, IL-1β (interleukin-1β), PAI-1 (plasminogen-activator inhibitor-1) and TNFα (tumour necrosis factor α) gene expression; and (vii) IκBα (inhibitor of nuclear factor κB α) protein expression. F-fed animals had high serum TAG (triacylglycerol), NEFA and insulin levels, high liver NADPH oxidase activity/expression, increased OS markers, reduced antioxidant enzyme expression, and increased glycogen, TAG storage and GK, G6Pase and G6PDH activities. They also had high G6Pase, G6PDH, FAS, GPAT, TNFα and IL-1β gene expression and decreased IκBα expression. Co-administration of apocynin to F-fed rats prevented the development of most of these abnormalities. In conclusion, NADPH oxidase plays a key role in F-induced hepatic OS production and probably also in the mechanism of liver steatosis, suggesting its potential usefulness for the prevention/treatment of T2DM (Type 2 diabetes mellitus).

Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat

2008 ◽  
Vol 294 (6) ◽  
pp. H2659-H2668 ◽  
Author(s):  
Vincent G. DeMarco ◽  
Javad Habibi ◽  
Adam T. Whaley-Connell ◽  
Rebecca I. Schneider ◽  
Randall L. Heller ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Hypertension ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Surface Area ◽  
Vascular Remodeling ◽  
Oxidase Activity ◽  
Pulmonary Vascular Remodeling ◽  
Nadph Oxidase Activity ◽  
Sd Rats

The transgenic (mRen2)27 (Ren2) rat overexpresses mouse renin in extrarenal tissues, causing increased local synthesis of ANG II, oxidative stress, and hypertension. However, little is known about the role of oxidative stress induced by the tissue renin-angiotensin system (RAS) as a contributing factor in pulmonary hypertension (PH). Using male Ren2 rats, we test the hypothesis that lung tissue RAS overexpression and resultant oxidative stress contribute to PH and pulmonary vascular remodeling. Mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), and wall thickness of small pulmonary arteries (PA), as well as intrapulmonary NADPH oxidase activity and subunit protein expression and reactive oxygen species (ROS), were compared in age-matched Ren2 and Sprague-Dawley (SD) rats pretreated with the SOD/catalase mimetic tempol for 21 days. In placebo-treated Ren2 rats, MAP and RVSP, as well as intrapulmonary NADPH oxidase activity and subunits (Nox2, p22phox, and Rac-1) and ROS, were elevated compared with placebo-treated SD rats ( P < 0.05). Tempol decreased RVSP ( P < 0.05), but not MAP, in Ren2 rats. Tempol also reduced intrapulmonary NADPH oxidase activity, Nox2, p22phox, and Rac-1 protein expression, and ROS in Ren2 rats ( P < 0.05). Compared with SD rats, the cross-sectional surface area of small PA was 38% greater ( P < 0.001) and luminal surface area was 54% less ( P < 0.001) in Ren2 rats. Wall surface area was reduced and luminal area was increased in tempol-treated SD and Ren2 rats compared with untreated controls ( P < 0.05). Collectively, the results of this investigation support a seminal role for enhanced tissue RAS/oxidative stress as factors in development of PH and pulmonary vascular remodeling.

Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction

2013 ◽  
Vol 125 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Juan Pablo Fariña ◽  
María Elisa García ◽  
Ana Alzamendi ◽  
Andrés Giovambattista ◽  
Carlos Alberto Marra ◽  
...  
Keyword(s):  
Drinking Water ◽  
Adipose Tissue ◽  
Nadph Oxidase ◽  
Plasma Levels ◽  
Oxidase Activity ◽  
Male Rats ◽  
Thiobarbituric Acid Reactive Substance ◽  
Model Assessment ◽  
Abdominal Adipose Tissue ◽  
Nadph Oxidase Activity

In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

scholarly journals ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice

2013 ◽  
Vol 305 (3) ◽  
pp. F323-F332 ◽  
Author(s):  
Bridget M. Ford ◽  
Assaad A. Eid ◽  
Monika Göőz ◽  
Jeffrey L. Barnes ◽  
Yves C. Gorin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Oxidase Activity ◽  
Matrix Protein ◽  
Enzyme Activation ◽  
Kidney Cortex ◽  
Diabetic Mice ◽  
Nadph Oxidase Activity ◽  
Matrix Accumulation

Matrix protein accumulation is a prominent feature of diabetic nephropathy that contributes to renal fibrosis and decline in renal function. The pathogenic mechanisms of matrix accumulation are incompletely characterized. We investigated if the matrix metalloprotease a disintegrin and metalloprotease1 7 (ADAM17), known to cleave growth factors and cytokines, is activated in the kidney cortex of OVE26 type 1 diabetic mice and the potential mechanisms by which ADAM17 mediates extracellular matrix accumulation. Protein expression and activity of ADAM17 were increased in OVE26 kidney cortex. Using a pharmacological inhibitor to ADAM17, TMI-005, we determined that ADAM17 activation results in increased type IV collagen, Nox4, and NADPH oxidase activity in the kidney cortex of diabetic mice. In cultured mouse proximal tubular epithelial cells (MCTs), high glucose increases ADAM17 activity, Nox4 and fibronectin expression, cellular collagen content, and NADPH oxidase activity. These effects of glucose were inhibited when cells were pretreated with TMI-005 and/or transfected with small interfering ADAM17. Collectively, these data indicate a novel mechanism whereby hyperglycemia in diabetes increases extracellular matrix protein expression in the kidney cortex through activation of ADAM17 and enhanced oxidative stress through Nox enzyme activation. Additionally, our study is the first to provide evidence that Nox4 is downstream of ADAM17.

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