scholarly journals Protection of Coenzyme Q-10 Against Contrast-induced Acute Kidney Injury in Diabetic Rats

2021 ◽  
Author(s):  
Sheila Marques Fernandes Couto ◽  
Cassiane Dezoti da Fonseca ◽  
Mirian Watanabe ◽  
Maria de Fátima Fernandes Vattimo
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Risk Factor ◽  
Coenzyme Q ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Renal Hemodynamics

Abstract Background: Diabetes Mellitus (DM) is a important risk factor for Contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI share oxidative damage and inflammation mechanisms that induction of protective and cellular adaptation enzymes as coenzyme Q-10 (COQ-10). The aim of this study was to investigate the therapeutic potential of COQ-10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats submitted to the CI-AKI model. Methods: Wistar rats, male, randomized into four groups: Citrate- control animals, received citrate buffer (streptozotocin vehicle, 0.4 ml); DM- animals that received streptozotocin (60 mg/kg); DM+IC: DM animals, treated with iodinated contrast (IC, 6 ml/kg); DM+IC+COQ-10: DM animals treated with COQ-10 (10 mg/kg) and that received with IC (6 ml/kg). The protocols lasted 4 weeks. Were evaluated the renal function by inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis.Results: DM animals showed reduced renal function which was reflected with an increase of serum creatinine and significant reduced of inulin clearance, as well as a reduction on RBF, increased RVR and redox imbalance with a higher urinary peroxides, nitrate lipid peroxidation levels and depletion of thiols in renal tissue. IC treatment exacerbated theses changes in DM + IC. COQ-10 administration ameliorates renal function, prevented hemodynamic changes, neutralize oxidative damage and progression of the histologic damage in the DM+IC+COQ-10 group. Conclusion: This study is the first that demonstrated a renoprotection of COQ-10 in experimental model of risk factor of DM for CI-AKI. COQ-10 presented an antioxidant effect on the CI-AKI in diabetic rats, by improving function and renal hemodynamics, preserving morphology and reducing oxidative stress.

scholarly journals Protection of coenzyme Q10 against contrast-induced acute kidney injury in male diabetic rats

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sheila Marques Fernandes Couto ◽  
Cassiane Dezoti da Fonseca ◽  
Mirian Watanabe ◽  
Maria de Fátima Fernandes Vattimo
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Risk Factor ◽  
Oxidative Damage ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Renal Hemodynamics

Abstract Background Diabetes mellitus (DM) is a major risk factor for contrast-induced acute kidney injury (CI-AKI). DM and CI-AKI result in oxidative damage and inflammation that can be reduced when treated with the coenzyme Q-10 (CoQ10). The aim of this study was to investigate the therapeutic potential of CoQ10 in renal function, renal hemodynamics, oxidative profile and renal histology in diabetic rats subjected to CI-AKI. Methods Wistar rats, male, randomized into five groups: citrate: control animals received citrate buffer (streptozotocin vehicle, 0.4 mL); Tween: control animals of CoQ10 treatment received 1% Tween 80 (CoQ10 vehicle, 0.5 mL); DM: animals that received streptozotocin (60 mg/kg); DM + IC: DM animals treated with iodinated contrast (IC, 6 mL/kg); DM + IC + CoQ10: DM animals treated with CoQ10 (10 mg/kg) and that received IC (6 mL/kg). The protocols lasted 4 weeks. An evaluation was made to measure renal function, inulin clearance and serum creatinine, renal hemodynamics by renal blood flow (RBF) and renal vascular resistance (RVR), markers of oxidative stress such as urinary peroxides and nitrate, lipid peroxidation, thiols in renal tissue and renal histological analysis. Results DM animals showed reduced renal function, which was followed by an increase inserum creatinine and significant reduction of inulin clearance and RBF. It was noticed an increase in RVR and redox imbalance with higher urinary peroxides and nitrate lipid peroxidation levels with depletion of thiols in renal tissue. IC treatment exacerbated these changes in DM + IC. CoQ10 administration ameliorated renal function, prevented hemodynamic changes and neutralized oxidative damage and progression of the histologic damage in the DM + IC + CoQ10 group. Conclusion This study demonstrated the renoprotection properties of CoQ10 in an experimental model of risk factor of DM for CI-AKI. CoQ10 presented an antioxidant effect on the CI-AKI in male diabetic rats by improving renal function and renal hemodynamics, preserving morphology and reducing 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.

scholarly journals A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Shuo Huang ◽  
Yanyan Tang ◽  
Tianjun Liu ◽  
Ning Zhang ◽  
Xueyan Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Superoxide Dismutase ◽  
Renal Function ◽  
Cytochrome C ◽  
Caspase 3 ◽  
Mitochondrial Protein ◽  
Kidney Injury ◽  
High Efficient ◽  
Superoxide Dismutase 2

Many studies proposed that oxidative stress and apoptosis are key mechanisms in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). Xylose-pyrogallol conjugate (XP) is an original effective antioxidant that showed decent antioxidant and anti-apoptosis effect before. Thus the therapeutic effect and mechanism of XP in preventing CI-AKI in the short and long term were investigated in this research. Renal function and histological grade were evaluated to determine the severity of renal injury. Kidney samples were then collected for the measurement of oxidative stress markers and the detection of apoptosis. Transmission electron microscopy (TEM) and western blot of mitochondrial protein were utilized for the analysis of the mitochondrial conditions. The results demonstrated that the CI-AKI rats caused a significant decrease in renal function accompanied by a remarkable increase in Malondialdehyde (MDA), bax, caspase-3, cytochrome c (Cyt C) level, TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and damaged mitochondria, while a decline in antioxidase activities and mitochondrial superoxide dismutase 2 (SOD2) expression compared with the control rats. However, when XP (50 or 100 or 200 mg/kg/day) was given orally for consecutive 7 days before CI-AKI modeling, XP (200 mg/kg) showed a better capability to restore renal dysfunction, histopathological appearance, the level of apoptosis, mitochondrial damage, oxidative stress, and fibrosis generation without interference in computed tomographic imaging. Our study indicated that antioxidant XP played a nephroprotective role probably via antiapoptotic and antioxidant mechanisms. Besides, XP may regulate the mitochondria pathway via decreasing the ratio of bax/bcl-2, inhibiting caspase-3 expression, cytochrome c release, and superoxide dismutase 2 activity. Overall, XP as a high-efficient antioxidant may have the potentials to prevent CI-AKI.

Troxerutin down-regulates KIM-1, modulates p38 MAPK signaling, and enhances renal regenerative capacity in a rat model of gentamycin-induced acute kidney injury

2018 ◽  
Vol 9 (12) ◽  
pp. 6632-6642 ◽  
Author(s):  
Samir A. Salama ◽  
Hany H. Arab ◽  
Ibrahim A. Maghrabi
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
P38 Mapk ◽  
Tissue Regeneration ◽  
Rat Model ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Mapk Signaling ◽  
Regenerative Capacity

Troxerutin enhances renal tissue regeneration, improves renal function, and decreases renal tissue injury in gentamycin-treated rats.

scholarly journals EFFECT OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA-AGONISTS ON DIABETES-INDUCED ACUTE KIDNEY INJURY: ROLE OF OXIDATIVE STRESS AND HYPERLIPIDEMIA

2019 ◽  
Vol 12 (1) ◽  
pp. 143
Author(s):  
Vishal Arvind Chakkarwar ◽  
Pravin Kawtikwar
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Single Dose ◽  
Lipid Profile ◽  
Density Lipoprotein ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

Objective: The present study investigated the possible effect of fenofibrate and gemfibrozil peroxisome proliferator-activated receptor-alpha agonist in diabetes-induced acute kidney injury (AKI) in rats.Methods: Rats were administered streptozotocin (STZ) (50 mg/kg, i.p., single dose) to induce experimental diabetes mellitus. The development of diabetic AKI was assessed biochemically and histologically. In addition, the diabetes-induced lipid profile and renal oxidative stress were assessed. The single dose of STZ produced diabetes, which induced renal oxidative stress, altered the lipid profile and subsequently produced kidney injuryAKI in 7 weeks by increasing serum creatinine, blood urea nitrogen (BUN), proteinuria, and glomerular damage. Treatment with fenofibrate and gemfibrozil (30 mg/kg p.o, 7 weeks) normalized the altered lipid profile by decreasing serum cholesterol, triglycerides, and increasing serum high-density lipoprotein in diabetic rats. Lisinopril (1 mg/kg, p.o., 7 weeks, reference compound) prevents lipid alteration and development of diabetic AKI.Result: Fenofibrate and gemfibrozil, besides hyperglycemia, significantly prevented the development of diabetic AKI by reducing (serum and tissue) oxidative stress, hyperlipidemia, serum BUN, creatinine, and urinary protein. Further, fenofibrate, but not gemfibrozil, considerably reduced renal structural and functional abnormalities in diabetic rats. The fenofibrate was more effective in attenuating the diabetes-induced AKI and renal oxidative stress as compared to treatment with and gemfibrozil.Conclusion: The fenofibrate and gemfibrozil treatment markedly prevented the diabetes-induced AKI. In comparison, the fenofibrate is found to be a superior approach to attenuate the diabetic AKI than gemfibrozil.

scholarly journals A Novel Contrast-Induced Acute Kidney Injury Model Based on the 5/6-Nephrectomy Rat and Nephrotoxicological Evaluation of Iohexol and IodixanolIn Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Tong-qiang Liu ◽  
Wei-li Luo ◽  
Xiao Tan ◽  
Yi Fang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Iodinated Contrast Media ◽  
Tubular Cells ◽  
Iodinated Contrast ◽  
Injury Model ◽  
Ablative Surgery ◽  
And Oxidative Stress

Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media. Proper animal models of CI-AKI can help understand the mechanisms involved and prevent the disorder. We used the 5/6-nephrectomized (NE) rat to develop a CI-AKI model and to evaluate differences in the toxic effects on the kidney between iohexol and iodixanol. We found that six weeks after ablative surgery was the preferred time to induce CI-AKI. We compared multiple pretreatment plans and found that dehydration for 48 hours before iodixanol (320, 10 mL/kg) administration was optimal to induce CI-AKI in the 5/6 NE rats. Compared with iodixanol, iohexol induced a significantly greater reduction in renal function, severe renal tissue damage, intrarenal hypoxia, and apoptotic tubular cells. Iohexol and iodixanol resulted in similarly marked increases in levels of inflammation and oxidative stress. In summary, the 5/6 NE rat combined with dehydration for 48 hours is a useful pretreatment to establish a novel and reliable CI-AKI model. Iohexol induced more severe CI-AKI than iodixanol in this model.

scholarly journals Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Pan Huang ◽  
Zhizhou Shen ◽  
Jia Liu ◽  
Yaqian Huang ◽  
Siyao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Antioxidative Activity ◽  
Kidney Injury ◽  
Renal Tissue ◽  
High Salt ◽  
Sod Activity ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sd Rats

Background. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats.Methods. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP), serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected.Results. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and•OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation.Conclusions. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress.

P0525ROLE OF NADPH OXIDASE 4 IN ACUTE KIDNEY INJURY ASSOCIATED TO MASSIVE INTRAVASCULAR HEMOLYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina García Caballero ◽  
Melania Guerrero Hue ◽  
Alejandra Palomino Antolín ◽  
Matilde Cabanillas ◽  
Cristina Vazquez Carballo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Wild Type ◽  
Intravascular Hemolysis ◽  
Nadph Oxidase 4

Abstract Background and Aims Massive intravascular hemolysis is a common condition of several pathologies. It is associated with acute kidney injury (AKI) and progressive impairment of renal function. In this context, free hemoglobin (Hb) can exert harmful effects by accumulating in the kidney, where induces oxidative stress and it becomes cytotoxic. NADPH oxidase 4 (Nox4) is the principal source of reactive oxygen species (ROS) in the kidney. Nox4 is mostly expressed in proximal tubular cells with lower levels in glomerulus. The role of Nox4 in renal damage is not clear, with studies reporting beneficial or deleterious actions depending of the environmental conditions. For that reason we aimed to investigate the role of Nox4 in massive intravascular hemolysis-associated AKI. Method To study the role of Nox4 in AKI caused by massive intravascular hemolysis, we performed an experimental model of intravascular hemolysis by intraperitoneal injection of phenylhydrazine (200 mg/kg) in wild type (Nox4+/+) and Nox4 knockout mice (Nox4-/-). Mice were sacrificed 24 and 72 hours after intravascular hemolysis induction. We collected serum, urine and tissues sample. We analyzed renal function, oxidative stress, cell death and inflammation in these samples. In other experiments, wild type mice were treated with GKT137831 (10mg/kg/day), a potent Nox4 and Nox1 inhibitor, and mice were sacrificed 72h after induction of hemolysis. We also performed in vitro experiments in murine tubular epithelial cells (MCT) and murine podocytes cells to investigate the regulation of Nox4 in Hb-stimulated cells treated or not with GKT137831. Results Induction of intravascular hemolysis in Nox4+/+ mice increased creatinine and BUN levels and enhanced the expression of tubular injury markers, such as NGAL. These pathological effects were reduced in Nox4 knockout mice. Then, we analyzed oxidative stress in our experimental model thought determination of HO-1, ferritin, GSH and lipid peroxidation levels. All of these oxidative markers were reduced in Nox4-/- mice with intravascular hemolysis as compared with Nox4+/+ mice. We also observed that inflammatory markers such as IL-6, cell death and podocytes injury markers were reduced in Nox4-/- mice than in wild type mice, specially 72 hours after phenylhydrazine injection. In line with these results, GKT137831 administration ameliorated intravascular hemolysis-associated renal function impairment. Moreover, oxidative stress, tubular injury markers and podocyte injury were reduced in hemolytic mice treated with GKT137831. GKT137831 also reduced Hb- and heme-mediated oxidative stress in MCT and podocytes. Conclusion Our results show the important role of Nox4 in renal injury associated to massive intravascular hemolysis. Moreover, the inhibition of Nox4 may be a potential therapeutic target to prevent renal damage associated to Hb accumulation. These findings provide new insights into novel aspects of Hb-toxicity and may have important pathogenic and therapeutic implications for intravascular hemolysis related diseases

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