scholarly journals Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Murat Olukman ◽  
Ebru Demirel Sezer ◽  
Sibel Ülker ◽  
Eser Y. Sözmen ◽  
Gülcihan Mehtap Çınar
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Thiobarbituric Acid ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fenofibrate Treatment ◽  
Streptozotocin Diabetic Rats ◽  
Total Homocysteine ◽  
Necrosis Factor

Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-αactivator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1day−1) for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-αlevel in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity.

scholarly journals Enhanced oxidative stress and endothelial dysfunction in streptozotocin-diabetic rats exposed to fine particles

2005 ◽  
Vol 99 (3) ◽  
pp. 335-343 ◽  
Author(s):  
Yu-Chen Lei ◽  
Jing-Shiang Hwang ◽  
Chang-Chuan Chan ◽  
Chung-Te Lee ◽  
Tsun-Jen Cheng
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Fine Particles ◽  
Diabetic Rats ◽  
Streptozotocin Diabetic 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.

Activation of peroxisome proliferator-activated receptor-β/-δ (PPARβ/δ) prevents endothelial dysfunction in type 1 diabetic rats

2012 ◽  
Vol 53 (4) ◽  
pp. 730-741 ◽  
Author(s):  
Ana María Quintela ◽  
Rosario Jiménez ◽  
Manuel Gómez-Guzmán ◽  
María José Zarzuelo ◽  
Pilar Galindo ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

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.

Natural Aldose Reductase Inhibitor: A Potential Therapeutic Agent for Non-alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 599-609 ◽  
Author(s):  
Longxin Qiu ◽  
Chang Guo
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Aldose Reductase ◽  
Fatty Liver Disease ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver

Aldose reductase (AR) has been reported to be involved in the development of nonalcoholic fatty liver disease (NAFLD). Hepatic AR is induced under hyperglycemia condition and converts excess glucose to lipogenic fructose, which contributes in part to the accumulation of fat in the liver cells of diabetes rodents. In addition, the hyperglycemia-induced AR or nutrition-induced AR causes suppression of the transcriptional activity of peroxisome proliferator-activated receptor (PPAR) α and reduced lipolysis in the liver, which also contribute to the development of NAFLD. Moreover, AR induction in non-alcoholic steatohepatitis (NASH) may aggravate oxidative stress and the expression of inflammatory cytokines in the liver. Here, we summarize the knowledge on AR inhibitors of plant origin and review the effect of some plant-derived AR inhibitors on NAFLD/NASH in rodents. Natural AR inhibitors may improve NAFLD at least in part through attenuating oxidative stress and inflammatory cytokine expression. Some of the natural AR inhibitors have been reported to attenuate hepatic steatosis through the regulation of PPARα-mediated fatty acid oxidation. In this review, we propose that the natural AR inhibitors are potential therapeutic agents for NAFLD.

scholarly journals Hydrogen Peroxide-Induced Inhibition of Vasomotor Activity: Evaluation of Single and Combined Treatments With Vitamin A and Insulin in Streptozotocin-Diabetic Rats

2002 ◽  
Vol 3 (2) ◽  
pp. 119-130 ◽  
Author(s):  
Fulya Zobali ◽  
Tanju Besler ◽  
Nuray Ari ◽  
Çimen Karasu
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Vitamin A ◽  
Diabetic Rats ◽  
Thiobarbituric Acid Reactive Substance ◽  
Single Treatment ◽  
Combined Treatments ◽  
Retinol Metabolism ◽  
Vasomotor Activity ◽  
Streptozotocin Diabetic Rats

A positive correlation has been established between increased oxidative stress and cardiovascular diseases in diabetes mellitus. We evaluated the effects of single or combined treatments with vitamin A (retinol acetate, 30 mg/kg/day, for 12-weeks) and insulin (8-10 IU/rat/day for the final 6-week) on vasomotor activity, oxidative stress and retinol metabolism in 12-week streptozotocin diabetic rats. The vasomotor activity was determined by measuring invitroresponsiveness of aorta rings to phenylephrine (PE) and acetylcholine (ACh) in the absence or in the presence of hydrogen peroxide (H2O2). Preincubation withH2O2(10 μM) produced a significant decrease in PE (1 mM)-induced contraction in untreated-diabetic but not in control rats. Single treatment with insulin counteracted this effect ofH2O2and also reversed the increased contractile response of diabetic aorta to PE, while vitamin A was found to be ineffective.H2O2(10 μM) also inhibited ACh (1 mM)-stimulated endothelium- dependent relaxation two fold more in diabetic than in control aorta. In the prevention ofH2O2-induced inhibition of vascular relaxation to ACh, vitamin A alone was markedly effective while insulin alone was not. The combination of vitamin A plus insulin removed the inhibitory action ofH2O2in diabetic aorta. Diabetic animals displayed an increased level of aorta thiobarbituric acid reactive substance (TBARS) in association with decreased levels of plasma retinol and retinol-binding protein (RBP). Single treatment with insulin, in spite of allowing recovery of normal growth rate and improved glucose and retinol metabolism in diabetic rats, was unable to control TBARS production to the same extent as vitamin A alone. Our findings suggest that the maintenance of ACh-stimulated endothelium-dependent vasorelaxant tone in normal physiological levels depends largely on the prevention and/or inhibition of peroxidative stress, which is achieved by combined treatment with vitamin A plus insulin. The use of vitamin A together with insulin provides a better metabolic control and more benefits than use of insulin alone in the reduction of diabetes-induced vascular complications.

scholarly journals Oxidative Stress in Rats After 60 Days of Hypergalactosemia or Hyperglycemia

2003 ◽  
Vol 22 (6) ◽  
pp. 423-427 ◽  
Author(s):  
Mary Otsyula ◽  
Matthew S. King ◽  
Tonya G. Ketcham ◽  
Ruth A. Sanders ◽  
John B. Watkins
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Glutathione Disulfide ◽  
Hepatic Lipid Peroxidation ◽  
Streptozotocin Diabetic Rats

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosy-lated hemoglobin A1c concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.

Sign in / Sign up

Export Citation Format

Share Document