UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress, that is, overproduction of reactive oxygen species and reduced antioxidant system activity, is implicated in the pathogenesis of diabetic complications; and therefore, superoxide dismutase (SOD) mimetic tempol should be protective in diabetic kidney. However, the effects of tempol in metabolic syndrome-associated renal injury have not been thoroughly examined. In this study, we examined the effects of 9 weeks of treatment with tempol on metabolic status, renal oxidative stress, and kidney function and structure in obese, diabetic, hypertensive ZSF(1) rats and their nondiabetic, hypertensive, lean littermates. The obese rats had significantly reduced total SOD and catalase activity, increased peroxidase activity and lipid peroxidation, and higher level of protein oxidation in renal cortical tissue compared with their lean littermates. These changes were accompanied by renal injury (proteinuria; reduced excretory function; and markedly increased glomerular and interstitial inflammation, proliferation, and collagen IV synthesis). Tempol treatment slightly increased total SOD activity, significantly reduced lipid peroxidation and peroxidase activity, but had no effect on catalase and protein oxidation. Tempol had no effects on blood pressure, renal hemodynamics and excretory function, and proteinuria in obese rats, yet improved insulin sensitivity and reduced renal inflammatory, proliferative, and fibrotic changes. Because tempol possesses no catalase activity and, in diabetes, not only SOD but also catalase is inhibited, it is possible that the toxicity of hydrogen peroxide (H(2)O(2)) remains unaltered under tempol treatment. This study suggests that superoxide and H(2)O(2) may have distinct roles in the pathogenesis of diabetic renal injury, with superoxide mainly being involved in inflammatory, proliferative, and fibrotic changes, and H(2)O(2) in glomerular hemodynamics and proteinuria.
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PMID:Renal and metabolic effects of tempol in obese ZSF1 rats--distinct role for superoxide and hydrogen peroxide in diabetic renal injury. 1880 50

Iron sucrose (Venofer; reference) has a good safety record and is prescribed in patients with anaemia and chronic kidney disease worldwide, but various iron sucrose similar (ISS) preparations are now utilized in clinical practice. This study evaluates possible differences between iron sucrose and ISS preparations on haemodynamic and oxidative stress markers in normal rats. 60 male and 60 female Sprague Dawley rats were divided into four groups and assigned to receive commercially available ISS test 1, ISS test 2, reference or isotonic saline solution (control). A single i.v. dose of iron (40 mg/kg) or saline (equivalent volume) was administered after 24 h and every 7 days for 4 weeks. Blood samples were collected for biological assessment of haemoglobin (Hb), serum iron and percentage transferrin saturation (TSAT), and urine samples were collected to investigate creatinine clearance and proteinuria. Animals were sacrificed after receiving an i.v. dose on days 1, 7 and 28, and kidney, liver, and heart homogenates were then collected to determine antioxidant enzyme levels. Tissues were processed using Prussian blue and immmunohistochemistry techniques to identify iron deposits, tissue ferritin and pro-inflammatory markers. Systolic blood pressure was significantly reduced in the ISS groups relative to the reference and control groups after 24 h and on days 7, 14 and 21 (p < 0.05). Creatinine clearance was reduced (p < 0.01) and proteinuria marked (p < 0.01) in the ISS groups at 24 h and on days 7 and 28 relative to the reference and control groups which did not differ throughout the study. Liver enzymes were also increased in the ISS groups at 24 h and on days 7 and 28. Both ISS test 1 and ISS test 2 groups presented a significant increase in catalase, thiobarbituric reactive species, Cu, Zn-superoxide dismutase (CuZnSOD) and glutathione peroxidase activity, and a decrease in glutathione levels (p < 0.01) in the liver, heart and kidney at 24 h and on day 7 relative to the reference and control groups. Serum iron and percentage TSAT were elevated in all groups (except control) (p < 0.01) but no differences in Hb concentration were observed between them. Finally, levels of the proinflammatory markers TNF-alpha and IL6 were significantly elevated in the ISS groups (liver, heart and kidney) compared with the reference and control groups on day 28 (p < 0.01). These findings suggest significant differences between the reference and ISS test 1/ISS test 2 regarding oxidative stress and the inflammatory responses of liver, heart and kidneys in normal rats. A possible explanation for these observations could be the stability of the iron complex.
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PMID:Differences between original intravenous iron sucrose and iron sucrose similar preparations. 1951 94

This study investigated the association between nephropathy and oxidative stress, by measurement of systolic blood pressure, lipid peroxidation, activities of catalase, manganese- and copper-zinc-superoxide dismutase and endothelial nitric oxide synthase expression and concentrations of nitrates/nitrites in kidneys from rats with Metabolic Syndrome. Weaning female or male rats had 30% sucrose to drink for 24 weeks (Metabolic Syndrome). Modulation by sex hormones was investigated by gonadectomy and hormone replacement. In Metabolic Syndrome, Castrated Metabolic Syndrome + Testosterone males and Ovariectomized Metabolic Syndrome females had increased blood pressure, proteinuria and lipid peroxidation. Nitrates/nitrites and activities of catalase, manganese and copper-zinc-superoxide dismutase decreased vs intact Control, Castrated Metabolic Syndrome males, intact Metabolic Syndrome and Ovariectomized Metabolic Syndrome + Estradiol females. The results suggest that sex hormones modulate the activity of superoxide-dismutase, catalase and endothelial nitric oxide-synthase. Ovariectomy decreased the protection against oxidative stress in females; the opposite occurred in castrated males.
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PMID:Association of renal damage and oxidative stress in a rat model of metabolic syndrome. Influence of gender. 1952 91

Accumulating clinical evidence indicates that impaired glucose tolerance is a common phenomenon in essential hypertension. Although recent evidence underscores the role of heme-oxygenase (HO) in diabetes, its effects on insulin sensitivity and glucose metabolism in spontaneously hypertensive rat (SHR), a model of essential hypertension with characteristics of metabolic syndrome including insulin resistance/impaired glucose metabolism remains largely unclear. Here we report the effects of the HO inducer, hemin, and the HO blocker, chromium-mesoporphyrin on insulin sensitivity and glucose metabolism in SHRs. Adult SHRs were severely hypertensive but normoglycemic. Hemin therapy lowered blood pressure, increased plasma insulin, decreased glycemia, and enhanced insulin sensitivity by improving glucose tolerance (ip glucose tolerance test) and insulin tolerance (ip insulin tolerance test) but reduced insulin resistance (homeostasis model assessment index). These effects were accompanied by increased gastrocnemius muscle HO-1, HO activity, cGMP, cAMP alongside antioxidants including bilirubin, ferritin, superoxide dismutase, catalase, and the total antioxidant capacity, whereas oxidative/inflammatory mediators like 8-isoprostane, nuclear-factor-kappaB, activating-protein-1, activating-protein-2, c-Jun-NH2-terminal-kinase, and heme were abated. Furthermore, hemin reduced proteinuria/albuminuria and enhanced the depressed levels of adiponectin, AMP-activated protein-kinase, and glucose transporter-4 in SHRs, suggesting that although SHRs are normoglycemic, insulin signaling and renal function may be impaired. Contrarily, the HO inhibitor chromium-mesoporphyrin exacerbated oxidative stress, aggravated insulin resistance, glucose tolerance, insulin tolerance and nephropathy. Hemin also enhanced HO signaling in Wistar Kyoto and Sprague Dawley rats and increased insulin sensitivity albeit less intensely than in SHRs, suggesting greater selectivity of HO in SHRs with dysfunctional insulin signaling. These results suggest that perturbations of insulin signaling may be a forerunner to hyperglycemia in essential hypertension. By concomitantly potentiating insulin-sensitizing agents, suppressing insulin/glucose intolerance, and abating oxidative stress, HO inducers may prevent metabolic and cardiovascular complications in essential hypertension.
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PMID:Up-regulating the heme oxygenase system with hemin improves insulin sensitivity and glucose metabolism in adult spontaneously hypertensive rats. 2001 31

The beneficial influences of xylo-oligosaccharides (XOS) obtained from alkali-pretreated corncob and fructo-oligosaccharides (FOS) obtained from cane sugar were evaluated in experimental diabetes. These oligosaccharides were supplemented at 10 % (w/w) in the basal diet of streptozotocin-induced diabetic Wistar rats, while the control rats were fed with a basal diet for a period of 6 weeks. Both the oligosaccharides exerted favourable influences in diabetic rats by significantly improving body weight and reducing hyperglycaemia and cholesterol. The characteristic diabetic complications such as severe glucosuria, proteinuria and advanced glycation end products in renal tissue, diabetic nephropathy, and blood creatinine and urea concentrations were notably reduced. Besides, these oligosaccharide supplementations significantly increased the activity of antioxidant enzymes - catalase and glutathione reductase - in the blood of diabetic rats. Supplementation of XOS and FOS resulted in a significant increase in the bifidobacteria and lactobacilli population in the caecum. The present study indicates that XOS and FOS have an ameliorating influence on metabolic abnormalities associated with diabetes, besides conferring an optimal milieu of lactobacilli and bifidobacteria, thus suggesting their potential health benefit in diabetics.
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PMID:Beneficial effect of xylo-oligosaccharides and fructo-oligosaccharides in streptozotocin-induced diabetic rats. 2018 88

To ascertain the onset of renal oxidative stress and its interrelation with the increase in blood pressure (BP) and kidney injury in rats subjected to Deoxycorticosterone (DOCA)-salt treatment, BP, renal antioxidants, renal damage indices, and histological changes were studied weekly. In the two other groups, 200 mg/kg/day vitamin E or C were co-administered with DOCA-salt for 4 weeks. Blood Pressure was increased at week one. Urinary N-acetyl-B-diglucosaminidase (NAG) and proteinuria increased and renal catalase decreased at 2nd week. Histological changes and decreased glothatione (GSH) and Ferric reducing antioxidant power (FRAP) were demonstrated at three week. Vitamin therapy increased renal antioxidants and decreased BP, NAG, proteinuria, and histological damage. Thus, elevation in BP precedes the onset of renal oxidative stress in DOCA-salt treated rats. Enhanced renal oxidative stress contributes to kidney damage. In this study, treatment with vitamin C or vitamin E preserved renal antioxidant levels, prevented renal damage, and partially inhibited elevation of BP in the DOCA-salt treatment.
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PMID:Evaluation of renal oxidative stress in the development of DOCA-salt induced hypertension and its renal damage. 2037 82

We investigated the role of heme oxygenase (HO), adiponectin, and atrial natriuretic peptide (ANP) in uninephrectomized (UnX) deoxycorticosterone-acetate (DOCA)-salt hypertensive rats, a volume-overload model characterized by elevated endothelin-1 (ET-1), mineralocorticoid-induced oxidative/inflammatory insults, fibrosis, hypertrophy, and severe renal histopathological lesions that closely mimic end-stage renal disease (ESRD). HO was enhanced with heme arginate (HA) or blocked with chromium mesoporphyrin (CrMP). Histological, morphological/morphometrical, quantitative reverse transcription-polymerase chain reaction, Western blot, enzyme immunoassay, and spectrophotometric analysis were used. Our experimental design included the following groups of rats: A, controls [surgery-free Sprague-Dawley, UnX-sham, UnX-salt (0.9% NaCl + 0.2% KCl), and UnX-DOCA]; B, UnX-DOCA-salt hypertensive; C, UnX-DOCA-salt + HA; D, UnX-DOCA-salt + HA + CrMP; E, UnX-DOCA-salt + CrMP; F, UnX-DOCA-salt + captopril; G, UnX-DOCA-salt + L-arginine; H, UnX-DOCA-salt + spironolactone; and I, UnX-DOCA-salt + vehicle. HA lowered blood pressure and abated kidney hypertrophy and renal lesions, including glomerulosclerosis, tubular dilation, tubular cast formation, interstitial mononuclear cell infiltration, glomerular hypertrophy, and renal-arteriolar thickening in UnX-DOCA hypertension. Correspondingly, HO activity, adiponectin, adenosine monophosphate-activated protein kinase (AMPK), ANP, cGMP, antioxidants such as bilirubin, ferritin, superoxide dismutase, and catalase, and total antioxidant capacity were increased, whereas ET-1, transforming growth factor beta (TGF-beta), fibronectin, and 8-isoprostane were abated. These were accompanied by reduced proteinuria/albuminuria, but increased creatinine clearance. Interestingly, HA was more renoprotective than sipronolactone, L-arginine, and captopril, whereas the HO blocker CrMP exacerbated oxidative injury, aggravating renal lesions and function. Because 8-isoprostane stimulates ET-1 to potentiate oxidative stress and fibrosis, up-regulating HO-1 enhanced tissue antioxidant status alongside cellular targets such as adiponectin, AMPK, ANP, and cGMP to suppress ET-1, TGF-beta, and fibronectin with a corresponding decline of renal lesions, proteinuria/albuminuria, and thus improved renal function. The potent renoprotection of HA could be explored to combat renal hypertrophy and histopathological lesions characteristic of ESRD.
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PMID:Heme arginate therapy enhanced adiponectin and atrial natriuretic peptide, but abated endothelin-1 with attenuation of kidney histopathological lesions in mineralocorticoid-induced hypertension. 2039 17

The mechanisms by which angiotensin-(1-7) [Ang-(1-7)] exerts its beneficial effects on end-organ damage associated with diabetes and hypertension are not well understood. The purpose of this study was A) to compare the effects of apocynin with Ang-(1-7) on renal vascular dysfunction and NADPH oxidase activity in a combined model of diabetes and hypertension and B) to further determine whether chronic treatment with Ang-(1-7) can modulate renal catalase, and peroxisome proliferator activated receptor- gamma (PPAR-gamma) levels in streptozotocin-induced diabetes in both normotensive Wistar Kyoto rats (WKY) and in spontaneously hypertensive rats (SHR). Apocynin or Ang-(1-7) treatment for one month starting at the onset of diabetes similarly attenuated elevation of renal NADPH oxidase activity in the diabetic SHR kidney and reduced the degree of proteinuria and hyperglycemia, but had little or modest effect on reducing mean arterial pressure. Both drugs also attenuated the diabetes-induced increase in renal vascular responsiveness to endothelin-1. Induction of diabetes in WKY and SHR animals resulted in significantly reduced renal catalase activity and in PPAR-gamma mRNA and protein levels. Treatment with Ang-(1-7) significantly prevented diabetes-induced reduction in catalase activity and the reduction in PPAR-gamma mRNA and protein levels in both animal models. Taken together, these data suggest that activation of Ang-(1-7)-mediated signaling could be an effective way to prevent the elevation of NADPH oxidase activity and inhibition of PPAR-gamma and catalase activities in diabetes and/or hypertension.
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PMID:Angiotensin-(1-7) prevents diabetes-induced attenuation in PPAR-gamma and catalase activities. 2044 91

Oxidative stress plays an important role in the pathogenesis of anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN). Superoxide dismutase (SOD) is the first line of defense against oxidative stress by converting superoxide to hydrogen peroxide (H(2)O(2)). We investigated the effect of the SOD mimetic drug tempol on anti-GBM-GN in mice. 129/svJ mice were challenged with rabbit anti-mouse-GBM sera to induce GN and subsequently divided into tempol (200 mg.kg(-1).day(-1), orally) and vehicle-treated groups. Routine histology, SOD and catalase activities, malondialdehyde (MDA), H(2)O(2), and immunohistochemical staining for neutrophils, lymphocytes, macrophages, p65-NF-kappaB, and osteopontin were performed. Mice with anti-GBM-GN had significantly reduced renal SOD and catalase activities and increased H(2)O(2) and MDA levels. Unexpectedly, tempol administration exacerbated anti-GBM-GN as evidenced by intensification of proteinuria, the presence of severe crescentic GN with leukocyte influx, and accelerated mortality in the treated group. Tempol treatment raised SOD activity and H(2)O(2) level in urine, upregulated p65-NF-kappaB and osteopontin in the kidney, but had no effect on renal catalase activity. Thus tempol aggravates anti-GBM-GN by increasing production of H(2)O(2) which is a potent NF-kappaB activator and as such can intensify inflammation and renal injury. This supposition is supported by increases seen in p65-NF-kappaB, osteopontin, and leukocyte influx in the kidneys of the tempol-treated group.
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PMID:Superoxide dismutase mimetic drug tempol aggravates anti-GBM antibody-induced glomerulonephritis in mice. 2050 83

IgA nephropathy (IgAN) is characterized by mesangial deposits of IgA1, likely due to accumulation of IgA immune complexes. The activation of intracellular signaling mostly results in oxidative stress, as detected in mesangial cells cultured with aberrantly glycosylated IgA or IgA aggregates and in renal biopsies of patients with IgAN. Signs of altered oxidation/antioxidation balance have been detected in sera and/or in erythrocytes of patients with IgAN, including increased levels of lipoperoxide or malondialdehyde and reduced activity of superoxide dismutase, catalase and glutathione peroxidase. Moreover, increased levels of a marker of oxidative stress, advanced oxidation protein products (AOPPs), have been reported to be significantly associated with proteinuria and disease progression in patients with IgAN. AOPPs are often carried by albumin and can in turn enhance the oxidative stress in the circulation. Recent research suggests that the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN is enhanced in the presence of systemic signs of oxidative stress, and it is tempting to hypothesize that the level of the oxidative milieu conditions the different expression and progression of IgAN.
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PMID:Oxidative stress in IgA nephropathy. 2060 79

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