8-epi-prostaglandin-f2alpha and Kidney-Diseases

Topics: Biomarkers; Cerebrovascular Disorders; Dinoprost; Humans; Hypercholesterolemia; Immunoenzyme Techniques; Inflammation; Kidney Diseases; Myocardial Ischemia; Oxidative Stress; Radioimmunoassay; Reference Values; Specimen Handling

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Benzimidazoles; Benzoates; Chronic Disease; Cilazapril; Creatinine; Cross-Over Studies; Dinoprost; Diuretics; Female; Humans; Hydrochlorothiazide; Kidney Diseases; Male; Mineralocorticoid Receptor Antagonists; Oxidative Stress; Spironolactone; Telmisartan

Tempol, a superoxide dismutase-mimetic drug, has been shown to attenuate radical-induced damage, exerting beneficial effects in the animal models of oxidative stress and hypertension. This study evaluated the effect of Tempol on renal structural and functional alterations in two-Kidney, one-Clip hypertensive rats. In this study, young male Wistar rats had the left kidney clipped (2K1C), and sham-operated animals (Sham) were used as controls. Animals received Tempol (1mmol/L in drinking water) or vehicle for 5 weeks. Systolic blood pressure was evaluated once a week. At the end of the experimental protocol, the animals were placed in metabolic cages to collect urine (24h) and then anesthetized with thiopental (70mg/kg i.p.) to collect blood by puncturing the descending aorta for biochemical analysis, and the clipped kidney for morphological and immunohistochemical analyses. The vasodilator effect of Tempol was evaluated in mesenteric arterial bed (MAB) isolated from adult Wistar rats. The chronic treatment with Tempol prevented the development of hypertension and the increased plasma levels of urea, creatinine, and 8-isoprostane in 2K1C animals. Tempol also improved both glomeruli number and kidney volume to normal levels in the 2K1C+Tempol group. In addition, the treatment prevented the increased collagen deposition and immunostaining for renin, caspase-3, and 8-isoprostane in the stenotic kidney of 2K1C animals. Moreover, Tempol induced a dose-dependent vasodilator response in MAB from Wistar rats. These results suggest that Tempol protects the stenotic kidney against chronic ischemic renal injury and prevents renal dysfunction in the 2K1C model, probably through its antioxidant, vasodilator and antihypertensive actions.

Topics: Animals; Antioxidants; Biomimetic Materials; Blood Pressure; Caspase 3; Chronic Disease; Creatinine; Cyclic N-Oxides; Dinoprost; Hypertension; Ischemia; Kidney; Kidney Diseases; Kidney Glomerulus; Male; Oxidative Stress; Rats; Rats, Wistar; Renin; Spin Labels; Superoxide Dismutase; Urea; Vasodilation

Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.. Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.. The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2.. Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

Topics: Acetaminophen; Analgesics; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cytokines; Dinoprost; Inflammation; Interleukin-1beta; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Platelet Activation; Rats; Rats, Wistar; Thromboxane B2; Tumor Necrosis Factor-alpha

The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria.

Topics: Actins; Adenosine; Adenosine A3 Receptor Antagonists; Albuminuria; Animals; Body Weight; Creatinine; Dinoprost; Disease Models, Animal; Doxorubicin; Immunohistochemistry; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; NF-kappa B; Oxidative Stress; Plasminogen Activator Inhibitor 1; Proteinuria; Transforming Growth Factor beta1

Anthocyanins are major constituents of food colours and have been reported to possess anti-diabetic activities for potential medicinal use. The precise role of anthocyanins in diabetic nephropathy is poorly understood. We investigated whether anthocyanin-rich Seoritae extract (SE) can potentially prevent oxidative stress and lipotoxicity, which are the main causes of renal damage in diabetic nephropathy, via activation of AMP-activated protein kinase (AMPK) and the consequent effects on its target molecules.. Four groups of male C57BLKS/J db/m and db/db mice were used. Diabetic and non-diabetic mice were orally administered 10 mg/kg body weight SE daily for 12 weeks, starting at 8 weeks of age.. db/db mice treated with anthocyanins showed decreased albuminuria. Anthocyanins ameliorated intra-renal lipid concentrations in db/db mice with improvement of glomerular matrix expansion and inflammation, which was related to increased phosphorylation of AMPK and activation of peroxisome proliferator-activated receptor (PPAR) α and PPARγ, and inhibited the activity of acetyl-CoA carboxylase and sterol regulatory element-binding protein 1. Anthocyanins reversed diabetes-induced increases in renal apoptosis and oxidative stress. In cultured human glomerular endothelial cells, anthocyanins prevented high glucose-induced oxidative stress and apoptosis through activation of AMPK in the same manner.. The results revealed that anthocyanins ameliorated diabetic nephropathy in db/db mice via phosphorylation of AMPK, the major energy-sensing enzyme, and the consequent effects on its target molecules, which appeared to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.

Topics: AMP-Activated Protein Kinases; Animals; Anthocyanins; Apoptosis; bcl-2-Associated X Protein; Cholesterol; Collagen Type IV; Diabetes Mellitus, Experimental; Dinoprost; Endothelial Cells; Enzyme Activation; Fatty Acids; Glycine max; Humans; Kidney; Kidney Diseases; Lipids; Male; Mice, Inbred C57BL; Oxidative Stress; Phenotype; Phosphorylation; Plant Extracts; Transforming Growth Factor beta; Triglycerides

Aging is associated with renal structural changes and functional decline. The attributable risk for renal dysfunction from radiocontrast agents in critically ill older patients has not been well established.. In this prospective study, we assessed the incidence of contrast-induced nephropathy (CIN) in critically ill patients with stable renal function who underwent computed tomography with intravenous contrast media. Patients were categorized into two age groups: <65 (YG) or ≥ 65 years old (OG). CIN was defined as 25% or greater increase from baseline of serum creatinine or as an absolute increase by 0.5 mg/dL until the 5th day after the infusion of contrast agent. We also evaluated the alterations in oxidative stress by assessing serum 8-isoprostane.. CIN occurred in 5 of 13 OG patients (38.46%) whereas no YG patient presented CIN (P = 0.015). Serum creatinine kinetics in older patients demonstrated a rise over five days following contrast infusion time while a decline was observed in the YG (P = 0.005).. Older critically ill patients are more prone to develop renal dysfunction after the intravenous infusion of contrast agent in relation to their younger counterparts.

Topics: Adult; Aging; Contrast Media; Creatinine; Critical Illness; Dinoprost; Female; Humans; Kidney Diseases; Male; Urea

Dipeptidyl peptidase IV (DPPIV) is an exopeptidase that modulates the function of several substrates, among which insulin-releasing incretin hormones are the most well known. DPPIV also modulate substrates involved in inflammation, cell migration, and cell differentiation. Although DPPIV is highly expressed in proximal renal tubular cells, the role of DPPIV inhibition in renal disease is not fully understood. For this reason, we investigated the effects of LC15-0444, a DPPIV inhibitor, on renal function in a mouse model of renal fibrosis. Eight-week-old C57/BL6 mice were subjected to unilateral ureteral obstruction (UUO) and were treated with LC15-0444 (a DPPIV inhibitor) at a dose of 150 mg/kg per day in food or vehicle for 14 days. DPPIV activity was significantly increased in obstructed kidneys, and reduced after treatment with LC15-0444. Administration of LC15-0444 resulted in a significant decrease in albuminuria, urinary excretion of 8-isoprostane, and renal fibrosis. DPPIV inhibition also substantially decreased the synthesis of several proinflammatory and profibrotic molecules, as well as the infiltration of macrophages. UUO significantly increased, and LC15-0444 markedly suppressed, levels of phosphorylated Smad2/3, TGFβ1, toll-like receptor 4, high-mobility group box-1, NADPH oxidase 4, and NF-κB. These results suggest that activation of DPPIV in the kidney has a role in the progression of renal disease and that targeted therapy inhibiting DPPIV may prove to be a useful new approach in the management of progressive renal disease, independent of mechanisms mediated by glucagon-like peptide-1.

Topics: Animals; Cytokines; Dinoprost; Dipeptidyl-Peptidase IV Inhibitors; Fibrosis; Kidney; Kidney Diseases; Mice; Mice, Inbred C57BL; Oxidative Stress; Piperidones; Proteinuria; Pyrimidines; Statistics, Nonparametric; Ureteral Obstruction

Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress.. In this study, we aimed to determine if vitamin D would suppress oxidative stress using 4 groups of hypertensive rats: uninephrectomized, stroke-prone, spontaneously hypertensive rats fed a high-salt (6%) diet (controls; C); those treated with irbesartan (I); those treated with calcitriol (V); and those treated with both irbesartan and calcitriol (I+V).. Systolic blood pressure was higher in the C group than in the I and I+V groups. Albuminuria was attenuated in groups I, V, and I+V. Renal angiotensin II (AngII) concentration was lower in groups I and I+V than in group C, and plasma AngII levels of groups I and V were higher and lower than those in group C, respectively. Compared with group C, renal klotho expression, 8-epi-prostaglandin F2α excretion, and acetylcholine-induced decrease in blood pressure improved in the V and I+V groups.. The data indicate that irbesartan effectively decreases blood pressure and renal AngII levels, and improves albuminuria. Our findings indicate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII levels. These results suggest that the amelioration of endothelium function by vitamin D involves free klotho.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Calcitriol; Dietary Supplements; Dinoprost; Disease Models, Animal; Endothelium, Vascular; Glucuronidase; Hypertension; Irbesartan; Kidney; Kidney Diseases; Klotho Proteins; Male; Oxidative Stress; Rats; Rats, Inbred SHR; Tetrazoles; Vasodilation; Vitamins

Oxidative stress plays an important role in the progression of renal interstitial fibrosis. The nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (Nox) family is considered one of the major sources of reactive oxygen species (ROS). In the present study, we investigated the inhibitory effects of a novel anti-fibrotic agent, Fluorofenidone (AKF-PD), upon Nox-mediated oxidative stress and deposition of extracellular matrix (ECM) in the development of renalinterstitial fibrosis.. AKF-PD was used to treat renal fibrosis in unilateral ureteral obstruction (UUO) obstructive nephropathy in rats. The expression of Nox homologues, p-Akt, collagen I and III were detected by immunoblotting or immunohistochemistry. Levels of 8-iso prostaglandin F2alpha (8-Iso PGF2a) was measured by enzyme linked immunosorbent assay. In addition, ROS and the expression of collagen I (1a), Nox subunits and p-Akt was measured in angiotensin (Ang) II-stimulated rat proximal tubular epithelial (NRK-52E) cells in culture.. AKF-PD treatment significantly attenuated tubulo-interstitial injury, ECM deposition and oxidative stress in fibrotic rat kidneys. In addition, AKF-PD inhibited the expression of ROS, Collagen I (1a), Nox2, p-Akt in Ang II-stimulated NRK-52E cells.. AKF-PD attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and ECM deposition via the PI3K/Akt signalling pathway, suggesting AKF-PD is a potential novel therapeutic agent against renal fibrosis.

Topics: Angiotensin II; Animals; Antioxidants; Cell Line; Class Ia Phosphatidylinositol 3-Kinase; Collagen Type I; Dinoprost; Disease Models, Animal; Enzyme Inhibitors; Fibrosis; Kidney Diseases; Kidney Tubules; Lipid Peroxidation; Losartan; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Phosphorylation; Proto-Oncogene Proteins c-akt; Pyridones; Rats; Rats, Sprague-Dawley; Signal Transduction; Transfection; Ureteral Obstruction

Advanced glycation end products (AGEs) are produced by glycoxidation and lipid peroxidation. AGEs induce oxidative stress and inflammation, and accumulate in tubular cells after kidney transplantation. We hypothesize that the AGE formation blocker aminoguanidine (AG) reduces AGE formation and improves renal transplant function.. Fisher 344 kidneys were orthotopically transplanted into Lewis recipients. Recipients were treated with AG (100 mg/kg/day), candesartan (CAND; 5mg/kg/day), or vehicle (VEH) for 24 weeks. The major non-cross linking AGE N(ε)-carboxymethyllysine (CML) was measured post-transplantation with gas chromatography-tandem mass spectrometry or immunohistochemistry. As a marker of systemic lipid peroxidation 8-isoprostane was measured by ELISA. We determined intra-arterial blood pressure, heart weight/body weight ratio, size of cardiomyocytes and cardiac hypertrophy as assessed by echocardiography. For biochemical evaluation of cardiac and renal fibrosis we measured hydroxyproline content.. AG significantly reduced serum CML and 8-isoprostane, but did not reduce signs of chronic allograft nephropathy (CAN) or blood pressure. AG did not alter tubular AGE accumulation. AG reduced heart weight/body weight ratio (AG: 2.7 ± 0.1g/kg; CAND: 2.2 ± 0.1, VEH: 3.0 ± 0.4 g/kg), size of cardiomyocytes (P < 0.05) and showed a tendency to reduce cardiac hypertrophy (wall volume average radial AG 7.072 ± 0.83 cm(3) vs. CAND 6.841 ± 0.66 cm(3) vs. VEH 7.839 ± 0.74 cm(3)).. Despite effective reduction of serum CML and 8-isoprostane, AG did not ameliorate CAN or reduce renal AGE accumulation. On the other hand AG reduced cardiac size suggesting a supportive cardio-protective action which is blood pressure independent.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Biphenyl Compounds; Cardiotonic Agents; Dinoprost; Enzyme Inhibitors; Glycation End Products, Advanced; Guanidines; Hydroxyproline; Kidney Diseases; Kidney Function Tests; Kidney Transplantation; Lysine; Male; Oxidative Stress; Proteinuria; Rats; Rats, Inbred F344; Rats, Inbred Lew; Tetrazoles; Time Factors; Transplantation, Homologous

The objective of the study was to determine the presence or levels of antibodies (Abs) against caspase-3 and their clinical relevance in systemic sclerosis (SSc). Anti-caspase-3 Ab was examined by enzyme-linked immunosorbent assay and immunoblotting. IgG anti-caspase-3 Ab levels in SSc patients were higher than in normal controls. SSc patients positive for IgG anti-caspase-3 Ab had significantly longer disease duration, more frequent presence of decreased %VC and %DLco, and elevated levels of serum immunoglobulin and erythrocyte sedimentation rates. IgG anti-caspase-3 Ab levels correlated positively with serum IgG levels, renal vascular resistance, and serum levels of 8-isoprostane. Immunoblotting analysis confirmed the presence of anti-caspase-3 Ab in sera from SSc patients. Caspase-3 enzymatic activity was inhibited by IgG isolated from SSc sera containing IgG anti-caspase-3 Ab. These results suggest that autoantibody against caspase-3 is generated in SSc and that this Ab is related to the severity of pulmonary fibrosis, vascular damage, and inflammation.

Topics: Adult; Apoptosis; Autoantibodies; Biomarkers; Caspase 3; Dinoprost; Female; Humans; Immunoglobulin G; Kidney Diseases; Male; Middle Aged; Predictive Value of Tests; Pulmonary Fibrosis; Renal Circulation; Scleroderma, Systemic; Vasculitis

Although cigarette smoking is known to be an important risk factor for renal disease, the mechanism by which smoking induces progressive renal disease in a healthy population has not been established. We hypothesized that oxidative stress (measured as 8-iso-prostaglandin F(2α), 8-iso-PGF2a), inflammation (highly sensitive C-reactive protein (CRP), hs-CRP) and nitric oxide may be associated with an alteration in the estimated glomerular filtration rate (eGFR) and proteinuria in otherwise healthy smokers. A total of 649 eligible subjects were classified according to their smoking status. Plasma NOx was measured using ozone-based chemiluminescence, urinary 8-iso-PGF2a was measured using enzyme immunoassay and serum hs-CRP was measured using a latex aggregation nephelometry method. The levels of 8-iso-PGF2a and hs-CRP increased in current smokers (P=0.001 and P=0.029, respectively), although there was not an increase in the NOx level. The prevalence of a high eGFR increased in light smokers (odds ratio (OR) 1.15 (95% confidence interval (CI), 0.61-2.17)) and heavy smokers (OR 2.33 (95% CI, 1.06-5.10)) when compared with non- and past smokers (P for trend=0.024). The multivariable-adjusted mean values of the eGFR in current smokers, reported from the lowest to the highest quintiles of hs-CRP levels, were 82.1, 85.1, 86.4 and 88.5 ml per min per 1.73 m² (P for trend=0.027). The mean values of proteinuria were 28.6, 34.6, 37.2 and 39.5 mg g⁻¹ creatinine (P for trend=0.003). The correlation coefficient between hs-CRP and eGFR was increased significantly (P=0.03) across non- (r=0.03), past (r=-0.17), light (r=0.13) and heavy smokers (r=0.31). In conclusion, cigarette smoking is a risk factor for renal function alteration in healthy smokers and is characterized by a high eGFR and a high urinary protein associated with an increase in the hs-CRP. This finding suggests that hs-CRP may help mediate the alteration of renal function in smokers.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Dinoprost; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Life Style; Male; Middle Aged; Nitric Oxide; Proteinuria; Smoking; Young Adult

Suppression of the renin-angiotensin system has proven efficacy for mitigation and treatment of radiation nephropathy, and it has been hypothesized that this efficacy is due to suppression of radiation-induced chronic oxidative stress. It is known that radiation exposure leads to acute oxidative stress, but direct evidence for radiation-induced chronic renal oxidative stress is sparse. We looked for evidence of oxidative stress after total-body irradiation in a rat model, focusing on the period before there is physiologically significant renal damage. No statistically significant increase in urinary 8-isoprostane (a marker of lipid peroxidation) or carbonylated proteins (a marker of protein oxidation) was found over the first 42 days after irradiation, while a small but statistically significant increase in urinary 8-hydroxydeoxy-guanosine (a marker of DNA oxidation) was detected at 35-55 days. When we examined renal tissue from these animals, we found no significant increase in either DNA or protein oxidation products over the first 89 days after irradiation. Using five different standard methods for detecting oxidative stress in vivo, we found no definitive evidence for radiation-induced renal chronic oxidative stress. If chronic oxidative stress is part of the pathogenesis of radiation nephropathy, it does not leave widespread or easily detectable evidence behind.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Urea Nitrogen; Bone Marrow Transplantation; Deoxyguanosine; Dinoprost; Electrophoresis, Polyacrylamide Gel; Immunohistochemistry; Kidney Diseases; Models, Animal; Oxidative Stress; Rats; Whole-Body Irradiation

To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure.. Seventy-three patients with PGD and 50 controls were enrolled in the study. They were sub-grouped into non-proliferative glomerulonephritis (NPGN) and proliferative glomerulonephritis (PGN). Levels of serum malondialdehyde (MDA), reactive nitrogen intermediates (RNI), plasma total homocysteine (tHcy), urine 8-isoprostane (8-IP), RBC thiols, glutathione-S-transferase (GST) and serum superoxide dismutase (SOD) were measured spectrophotometrically.. PGD patients showed a significant increase in MDA, RNI, tHcy, 8-IP levels (P < 0.05) and decreased SOD, total thiols and protein bound thiol levels as compared to controls (P < 0.05). Significantly higher levels of tHcy, MDA and 8-IP (P < 0.05) and lower SOD enzyme activity (P < 0.05) were observed in PGN group as compared to NPGN and control groups. These changes remained significant even after adjustment was made for creatinine.. Oxidative stress in PGN is significantly higher than NPGN, indicating higher oxidative stress in these patients, independent of degree of renal dysfunction.

Topics: Adolescent; Adult; Animals; Dinoprost; Glomerulonephritis; Homocysteine; Humans; Kidney Diseases; Kidney Glomerulus; Malondialdehyde; Middle Aged; Oxidative Stress; Reactive Nitrogen Species

Angiotensin II (Ang II)-induced renal damage is associated with perivascular inflammation and increased oxidative stress. We tested the hypothesis whether entacapone, a catechol-O-methyltransferase (COMT) inhibitor exerting antioxidative and anti-inflammatory properties, protects against the Ang II-induced inflammatory response and end-organ damage.. Samples from double-transgenic rats harbouring human renin and human angiotensinogen genes (dTGR) and normotensive Sprague-Dawley rats (SD) were assessed by light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR), and high pressure liquid chromatography. The effects of entacapone treatment for 3 weeks were examined in dTGR and SD.. Entacapone completely prevented cardiovascular mortality and decreased albuminuria by 85% in dTGR. Entacapone ameliorated Ang II-induced vascular and glomerular damage, leucocyte infiltration, and intercellular adhesion molecule-1 (ICAM-1) overexpression in the kidneys. Serum 8-isoprostane concentration, as well as renal nitrotyrosine and 8-hydroxydeoxyguanosine expressions, all markers of oxidative stress, were markedly increased in dTGR and normalized by entacapone. Entacapone also decreased p22phox mRNA expression in the kidney. COMT expression was increased by 500% locally in the renal vascular wall in dTGR; however, COMT activity in the whole kidney remained unchanged. Urinary dopamine excretion, a marker of renal dopaminergic tone, was decreased by 50% in untreated dTGR. Even though entacapone decreased renal COMT activity by 40%, the renal dopaminergic tone remained unchanged in entacapone-treated dTGR.. Our findings suggest that entacapone provides protection against Ang II-induced renal damage through antioxidative and anti-inflammatory mechanisms, rather than by COMT inhibition-induced changes in renal dopaminergic tone.

Topics: Angiotensin II; Animals; Animals, Genetically Modified; Biomarkers; Blood Pressure; Cardiomegaly; Catechol O-Methyltransferase; Catechols; Creatinine; Dinoprost; Disease Models, Animal; Dopamine; Enzyme Inhibitors; Hypertension; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Diseases; Leukocytes; Male; Models, Cardiovascular; Nitriles; Norepinephrine; Rats; Rats, Sprague-Dawley; RNA, Messenger