Downregulation of vitamin C transporter SVCT-2 in doxorubicin-induced cardiomyocyte injury

2012 ◽  
Vol 303 (6) ◽  
pp. C645-C653 ◽  
Author(s):  
Ana R. Ludke ◽  
Anita K. Sharma ◽  
Gauri Akolkar ◽  
Gunjan Bajpai ◽  
Pawan K. Singal
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Vitamin C ◽  
Control Culture ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Apoptosis ◽  
Endogenous Antioxidant ◽  
Antioxidant Reserve ◽  
Vit C

Vitamin C (Vit C) has been shown to be protective against doxorubicin (Dox)-induced cardiotoxicity. However, Vit C uptake into cardiomyocytes is poorly understood. Furthermore, whether the antioxidant enzyme reserve is enhanced by Vit C is also not known. The present study investigated an influence of Dox on Vit C transporters, expression of endogenous antioxidant reserve as well as enzymes, oxidative stress, and apoptosis in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were exposed to control (culture medium 199 alone), Dox (10 μM), Vit C (25 μM), and Vit C + Dox for 24 h. Vit C transporter expression and localization, oxidative stress, antioxidant enzymes, and apoptosis were studied. Expression and localization of sodium-dependent vitamin C transporter-2 (SVCT-2) in the sarcolemma was reduced by Dox, but Vit C supplementation was able to blunt this change. There was a decrease in the expression of antioxidant enzymes glutathione peroxidase (GPx), catalase, and Cu/Zn superoxide dismutase (SOD) due to Dox, but only GPx expression was completely prevented and Cu/Zn SOD was partially rescued by Vit C. Dox-induced decrease in antioxidant reserve and increase in oxidative stress were partially mitigated by Vit C. Dox-induced apoptosis was ameliorated by Vit C. It is suggested that cardioprotection offered by Vit C in Dox-induced cardiomyopathy may involve an upregulation of SVCT-2 transporter followed by a reduction in oxidative stress as well as blunting of cardiomyocyte injury.

Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injuryThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.

2007 ◽  
Vol 85 (3-4) ◽  
pp. 439-443 ◽  
Author(s):  
Dinender K. Singla ◽  
Kuljeet Kaur ◽  
Anita K. Sharma ◽  
Sanjiv Dhingra ◽  
Pawan K. Singal
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Sprague Dawley ◽  
Isolated Hearts ◽  
Sprague Dawley Rats ◽  
Endogenous Antioxidant ◽  
Antioxidant Reserve

The present study examines whether a subchronic probucol treatment of rats offers protection against ischemia–reperfusion (IR) injury in isolated perfused hearts. Sprague–Dawley rats were treated every second day per week with probucol (cumulative dose 120 mg/kg body mass, i.p.) for 4 weeks. In the probucol group, baseline myocardial antioxidant enzyme, glutathione peroxidase (GSHPx), activity was increased (p < 0.05), whereas superoxide dismutase (SOD) and catalase (CAT) activities were not changed. Baseline oxidative stress, as indicated by the myocardial lipid peroxidation, was less (p < 0.05) in the probucol group. Isolated hearts were subjected to 60 min global I and 20 min R. Recovery of the contractile function in globally ischemic hearts upon reperfusion was 36% in untreated group and 74% in the probucol group. After IR, GSHPx and CAT activities were significantly (p < 0.05) higher in the probucol group compared with the control group, whereas SOD did not change. Lipid peroxidation owing to IR was significantly less in the probocol group. These data suggest that probucol treatment improves endogenous antioxidant reserve and protects against increased oxidative stress following IR injury.

scholarly journals The effect of Vitamin C on amodiaquine‐induced oxidative stress in the ovary of Sprague‐Dawley rats

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Stella C Gbotolorun ◽  
Abraham A Osinubi ◽  
Ademola A Oremosu ◽  
Cressie C Noronha ◽  
Amabe o Akpantah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin C ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria

2008 ◽  
Vol 295 (5) ◽  
pp. F1431-F1439 ◽  
Author(s):  
Edilia Tapia ◽  
Dolores J. Sánchez-González ◽  
Omar N. Medina-Campos ◽  
Virgilia Soto ◽  
Carmen Ávila-Casado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Inflammatory Cell ◽  
Pyrrolidine Dithiocarbamate ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Glomerular Hypertension ◽  
Markers Of Oxidative Stress ◽  
Glomerular Hemodynamics ◽  
Reduced Activity

We evaluated whether the blockade of the proinflammatory transcription factor NF-κB would modify the oxidative stress, inflammation, and structural and hemodynamic alterations found in the kidney as a result of massive proteinuria. Twenty male Sprague-Dawley rats were injected with 2 g of BSA intraperitoneally daily for 2 wk. Ten of them received in addition the inhibitor of NF-κB activation pyrrolidine dithiocarbamate (PDTC; 200 mg·kg−1·day−1 sc) and the rest received vehicle. Seven rats that received intraperitoneal saline were used as controls. Glomerular hemodynamics were studied after 14 days. Markers of oxidative stress (NF-κB subunit p65+ cells, 3-nitrotyrosine, and 4-hydroxynonenal), inflammation (cortical CD68+ cells and NOS-II), and afferent arteriole damage were assessed by immunohistochemistry and morphometry. Activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was evaluated in renal cortex and medulla. Albumin overload induced massive proteinuria, oxidative stress with reduced activity of antioxidant enzymes, NF-κB activation, inflammatory cell infiltration, a significant presence of proteinaceous casts, systemic and glomerular hypertension, as well as arteriolar remodeling. Treatment with PDTC prevented or improved all of these findings. In this model of nephrotic syndrome, we demonstrate a key role for oxidative stress and inflammation in causing systemic and glomerular hypertension and proteinuria. Oxidative stress and inflammation may have a key role in accelerating renal injury associated with intense proteinuria.

Effects of Dietary Supplements on Space Radiation-Induced Oxidative Stress in Sprague-Dawley Rats

2004 ◽  
Vol 162 (5) ◽  
pp. 572-579 ◽  
Author(s):  
Jun Guan ◽  
X. Steven Wan ◽  
Zhaozong Zhou ◽  
Jeffrey Ware ◽  
Jeremiah J. Donahue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dietary Supplements ◽  
Space Radiation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Radiation Induced

Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

2007 ◽  
Vol 292 (2) ◽  
pp. F861-F867 ◽  
Author(s):  
Melvin R. Hayden ◽  
Nazif A. Chowdhury ◽  
Shawna A. Cooper ◽  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Proximal Tubule ◽  
Structural Damage ◽  
Kidney Tissue ◽  
Proximal Tubule Cell ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

scholarly journals Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock

2016 ◽  
Vol 311 (1) ◽  
pp. G180-G191 ◽  
Author(s):  
Geeta Rao ◽  
Vivek R. Yadav ◽  
Shanjana Awasthi ◽  
Pamela R. Roberts ◽  
Vibhudutta Awasthi
Keyword(s):  
Oxidative Stress ◽  
Hemorrhagic Shock ◽  
Multiorgan Failure ◽  
Sprague Dawley ◽  
Barrier Dysfunction ◽  
Protective Mechanisms ◽  
Unfolded Protein ◽  
Sprague Dawley Rats ◽  
Markers Of Oxidative Stress ◽  
Protein Response

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms.

Dietary exposure to silver nanoparticles in Sprague–Dawley rats: Effects on oxidative stress and inflammation

2013 ◽  
Vol 60 ◽  
pp. 297-301 ◽  
Author(s):  
R. Ebabe Elle ◽  
S. Gaillet ◽  
J. Vidé ◽  
C. Romain ◽  
C. Lauret ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Silver Nanoparticles ◽  
Dietary Exposure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Energetics and mammary carcinogenesis: effects of moderate-intensity running and energy intake on cellular processes and molecular mechanisms in rats

2009 ◽  
Vol 106 (3) ◽  
pp. 911-918 ◽  
Author(s):  
Zongjian Zhu ◽  
Weiqin Jiang ◽  
John N. McGinley ◽  
Henry J. Thompson
Keyword(s):  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Mammary Carcinogenesis ◽  
Mitochondrial Pathway ◽  
Moderate Intensity ◽  
Free Access ◽  
Sprague Dawley ◽  
Cellular Processes ◽  
Sprague Dawley Rats ◽  
Induced Apoptosis

The objective of this experiment was to determine the effects on mammary carcinogenesis of similar limitations in energy availability either by energy expenditure due to moderate-intensity running (physical activity, PA) or by regulating dietary energy (RE) intake relative to a sedentary control (SC) group that ate ad libitum. A total of 90 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either SC, a PA group given free access to a motorized running wheel, or a RE group whose food intake limited growth to the rate observed in PA. Compared with SC, mammary carcinogenesis was inhibited by RE or PA. Cancer incidence, 92.6%, 77.8%, and 66.7% ( P = 0.06), and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat ( P = 0.006), in SC, RE, and PA, respectively, were reduced to a similar extent by RE and PA. Histological and Western blot analyses of mammary carcinomas provided evidence that RE and PA induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G1/S transition, and that intratumoral blood vessel density was reduced, although it remains to be determined whether PA and RE exert these effects via the same mechanisms.

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