scholarly journals Recurrent insulin-induced hypoglycemia induces AngII and COX2 leading to renal (pro)renin receptor expression and oxidative stress

2017 ◽  
Vol 5 (1) ◽  
pp. 71 ◽  
Author(s):  
Wael Alanazi ◽  
Mohammad Uddin ◽  
Selim Fakhruddin ◽  
Keith Jackson
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Kidney Injury ◽  
Organ Damage ◽  
Day Surgery ◽  
Receptor Expression ◽  
Sprague Dawley ◽  
Subunit Expression ◽  
Renal Biomarker ◽  
And Oxidative Stress

Background: Recurrent insulin-induced hypoglycemia (RIIH) is an avoidable consequence in the therapeutic management of diabetes mellitus. RIIH has been implicated in causing hypertension through an increase in renal and systemic AngII production.Objective: The present study was performed to assess the hypothesis that chronic insulin treatment enhances AngII and COX2 formation which in turn increases (pro) renin receptor (PRR) expression and NADPH oxidase-mediated oxidative stress, leading to renal and cardiac injury.Methods: The present studies were conducted in Male Sprague Dawley rats treated with daily subcutaneous injections of 7u/kg insulin or saline for 14 days. On the 14th day, surgery was performed for treatment infusion (captopril 12mg/kg, NS398 0.3mg/kg or vehicle), and renal interstitial fluid sample and urine collections for biomarker measurements. At the end of the experiments, kidneys and hearts were harvested to evaluate PRR and NOX2 (NADPH oxidase subunit) expression and oxidative stress.Results: We found that RIIH enhanced AngII and COX2 activity, leading to renal PRR expression and NADPH oxidase-induced oxidative stress in the heart and kidney. 8-isoprostane was evaluated as a renal biomarker of oxidative stress, which was induced in insulin treated animals and modulated by captopril and NS398. In addition, there was a slight increase in NGAL, a urinary biomarker of acute kidney injury (AKI), in insulin treated animals when compared to control.Conclusion: These results demonstrate that RIIH induces renal PRR expression and oxidative stress through increasing AngII and COX2 in the heart and kidney, leading to end-organ damage.

scholarly journals Resveratrol Supplementation Protects Against Nicotine-Induced Kidney Injury

2019 ◽  
Vol 16 (22) ◽  
pp. 4445 ◽  
Author(s):  
Ramalingam ◽  
Santhanathas ◽  
Shaukat Ali ◽  
Zainalabidin
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Prolonged Exposure ◽  
Kidney Injury ◽  
Receptor Blocker ◽  
Renal Diseases ◽  
Angiotensin Ii Receptor Blocker ◽  
Type I ◽  
Sprague Dawley ◽  
And Oxidative Stress

Prolonged exposure to nicotine accelerates onset and progression of renal diseases in habitual cigarette smokers. Exposure to nicotine, either via active or passive smoking is strongly shown to enhance renal oxidative stress and augment kidney failure in various animal models. In this study, we investigated the effects of resveratrol supplementation on nicotine-induced kidney injury and oxidative stress in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg, i.p.) alone or in combination with either resveratrol (8 mg/kg, i.p.), or angiotensin II type I receptor blocker, irbesartan (10 mg/kg, p.o.) for 28 days. Upon completion of treatment, kidneys were investigated for changes in structure, kidney injury markers and oxidative stress. Administration of nicotine alone for 28 days resulted in significant renal impairment as shown by marked increase in plasma creatinine, blood urea nitrogen (BUN) and oxidative stress. Co-administration with resveratrol however successfully attenuated these changes, with a concomitant increase in renal antioxidants such as glutathione similar to the conventionally used angiotensin II receptor blocker, irbesartan. These data altogether suggest that targeting renal oxidative stress with resveratrol could alleviate nicotine-induced renal injury. Antioxidants may be clinically important for management of renal function in habitual smokers.

Targeting Inflammation and Oxidative Stress as a Therapy for Ischemic Kidney Injury

2020 ◽  
Vol 85 (12-13) ◽  
pp. 1591-1602
Author(s):  
N. V. Andrianova ◽  
D. B. Zorov ◽  
E. Y. Plotnikov
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
And Oxidative Stress

scholarly journals Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 769
Author(s):  
Patoomporn Prasatthong ◽  
Sariya Meephat ◽  
Siwayu Rattanakanokchai ◽  
Juthamas Khamseekaew ◽  
Sarawoot Bunbupha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Tissue ◽  
Sprague Dawley ◽  
High Fat ◽  
Impaired Liver Function ◽  
Impaired Liver ◽  
Cardiometabolic Disorders ◽  
Cox 2 ◽  
Factor Α ◽  
And Oxidative Stress

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague–Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

scholarly journals Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-lei Wang ◽  
Tuo Zhang ◽  
Liu-hua Hu ◽  
Shi-qun Sun ◽  
Wei-feng Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Lipid Lowering ◽  
Control Group ◽  
Sprague Dawley ◽  
Atorvastatin Group ◽  
New Strategy ◽  
Ameliorative Effect ◽  
Markers Of Oxidative Stress

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.

Abstract 16443: Effects of Dietary Salt Intakes on Blood Pressure, Renal Function and Oxidative Stress in Rats Treated With Candesartan

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gangyi Zhu ◽  
Yanting Yu ◽  
Xiaoyan Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Renal Function ◽  
Kidney Diseases ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Low Salt ◽  
Receptor Blockers ◽  
And Oxidative Stress

Candesartan is one of angiotensin II type1 receptor blockers(ARB) and commonly used as first-line antihypertensive treatment. Low salt diet is often recommended by clinicians to the patients with hypertension and kidney diseases. However,it is not clear whether salt restriction is beneficial to the patients taking ARB. In order to explore this problem, the impacts of different salt diets on blood pressure (BP),renal function and oxidative stress were determined in 2-3 months old male Sprague Dawley rats treated with candesartan. The rats were randomly divided into 4 groups fed agar-gelled food rationally with NaCl content at 0.01%, 0.8%, 2% and 4% respectively(4-7 rats/group) while all rats were intraperitoneally injected with candesartan at 1mg / kg / day for 7 days. SBP started to decline on day 2 in all except 4% NaCl groups relative to day 0 (recorded 5-6 hrs before the first injection). On day 6, systolic BP (mmHg, tail-cuff, Softron,BP-98A) was lower in 0.8% (103.7+2.3) & 0.01% (101.6+3) groups than 2% (113.5+4.1) & 4% (129.9+4.6) groups (one way ANOVA,LSD test, P<0.05) and correlated positively with food NaCl intakes (R 2 =0.9832). DBP was changed in a similar pattern as SBP. Serum creatinine (μmol/L) was higher in 0.01% group (225+39) than groups of 0.8% (1328+350), 2% (2095+242) and 4% (1576+703) while creatinine clearance (ml/day) was lower in 0.01% group (69.3+9) than groups of 0.8% (43.7+9), 2%(27.7+2) and 4%(29+0.6). In order to determine whether oxidative stress plays any role in the BP regulation and renal function maintenance, we also checked renal protein expression of ROS components. Relative to 0.8% group, renal NOXs were not altered in 0.01% group while NOX1 (145+18,% of 0.8% group), NOX2 (240+54) and NOX4 (197+41) was higher in 2% group than other groups. Mn-SOD (77+7.8), not Cu-Zn SOD, was decreased while HO1 (170+16), not HO2, was increased in 0.01% group. Renal abundance of nitrotyrosine was lower in 0.01% than other groups indicating a decreased oxidative stress, possibly caused by increase in HO1. We concluded that salt restriction with candesartan is beneficial to antihypertensive effect of AT1R blockade but disadvantage to maintenance of renal function. Thus, cautions to choice of low salt intakes are necessary when taking ARB agents.

Abstract 305: Nebivolol Confers Mitochondria-Targeted Cardioprotection in Isoproterenol-Induced Acute Stressor State

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Sumeet S Vaikunth ◽  
Karl T Weber ◽  
Syamal K Bhattacharya
Keyword(s):  
Oxidative Stress ◽  
Cardiac Tissue ◽  
Mitochondrial Permeability Transition ◽  
Therapeutic Potential ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Antioxidant Defenses ◽  
Sprague Dawley ◽  
Acute Stressor ◽  
And Oxidative Stress

Introduction: Isoproterenol-induced acute stressor state simulates injury from burns or trauma, and results in Ca 2+ overloading and oxidative stress in diverse tissues, including cardiac myocytes and their subsarcolemmal mitochondria (SSM), overwhelming endogenous Zn 2+ -based antioxidant defenses. We hypothesized that pretreatment with nebivolol (Nebi), having dual beta-1 antagonistic and novel beta-3 receptor agonistic properties, would prevent Ca 2+ overloading and oxidative stress and upregulate Zn 2+ -based antioxidant defenses, thus enhancing its overall cardioprotective potential in acute stressor state. Methods: Eight-week-old male Sprague-Dawley rats received a single subcutaneous dose of isoproterenol (1 mg/kg) and compared to those treated with Nebi (10 mg/kg by gavage) for 10 days prior to isoproterenol. SSM were harvested from cardiac tissue at sacrifice. Total Ca 2+ , Zn 2+ and 8-isoprostane levels in tissue, and mitochondrial permeability transition pore (mPTP) opening, free [Ca 2+ ] m and H 2 O 2 production in SSM were monitored. Untreated, age-/sex-matched rats served as controls; each group had six rats and data shown as mean±SEM. Results: Compared to controls, isoproterenol rats revealed: (1) Significantly (*p<0.05) increased cardiac tissue Ca 2+ (8.2±0.8 vs. 13.7±1.0*, nEq/mg fat-free dry tissue (FFDT)), which was abrogated ( # p<0.05) by Nebi (8.9±0.4 # ); (2) Reduced cardiac Zn 2+ (82.8±2.4 vs. 78.5±1.0*, ng/mg FFDT), but restored by Nebi (82.4±0.6 # ); (3) Two-fold rise in cardiac 8-isoprostane (111.4±13.7 vs. 232.1±17.2*, pmoles/mg protein), and negated by Nebi (122.3+14.5 # ); (4) Greater opening propensity for mPTP that diminished by Nebi; (5) Elevated [Ca 2+ ] m (88.8±2.5 vs. 161.5±1.0*, nM), but normalized by Nebi (93.3±2.7 # ); and (6) Increased H 2 O 2 production by SSM (97.4±5.3 vs. 142.8±7.0*, pmoles/mg protein/min), and nullified by Nebi (106.8±9.0 # ). Conclusions : Cardioprotection conferred by Nebi, a unique beta-blocker, prevented Ca 2+ overloading and oxidative stress in cardiac tissue and SSM, while simultaneously augmenting antioxidant capacity and promoting mPTP stability. Therapeutic potential of Nebi in patients with acute stressor states remains a provocative possibility that deserves to be explored.

CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

2021 ◽  
pp. 153537022110471
Author(s):  
Junxia Zhang ◽  
Xue Lin ◽  
Jinxiu Xu ◽  
Feng Tang ◽  
Lupin Tan
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Sprague Dawley ◽  
Protein Levels ◽  
And Oxidative Stress

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

scholarly journals Enteral Baicalin, a Flavone Glycoside, Reduces Indicators of Cardiac Surgery-Associated Acute Kidney Injury in Rats

2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Injury Index ◽  
Sprague Dawley Rats

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.

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