Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Paliege, Alexander; Parsumathy, A.; Mizel, Diane; Yang, Tianxin; Schnermann, J.; Bachmann, S.

doi:10.1152/ajpregu.00219.2005

Cited by 36 publications

(35 citation statements)

References 40 publications

(54 reference statements)

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“…the increased 8-isoprostane excretion was the result of raised NAD(P)H oxidase activity, a further group of rats was treated with apocynin (19) and subjected to the raised sodium intake. Apocynin has been shown to interfere with the protein complexing of the NAD(P)H oxidase subunits, thereby interfering and decreasing its activity (9,19).…”

Section: Discussionmentioning

confidence: 99%

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Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Johns

O’Shaughnessy

O'Neill

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Pathophysiological states, including cardiovascular and renal diseases, are characterized by oxidative stress but what is less clear is whether physiological challenges incur a degree of altered oxidative metabolism. To this end, this study examined whether exposure to a high dietary sodium intake could cause an oxidative stress at the kidney. Animals, placed on either 0.3% or 3% sodium diets for 2 wk, were given a lethal dose of anesthetic, and kidneys were removed to analyze both NAD(P)H oxidase (NOX) and superoxide dismutase (SOD) expression and activities in the cortex and medulla. Placing animals on the highsodium diet raised sodium and water excretion and caused an ϳ14-fold increase in urinary excretion of 8-isoprostane, a marker of oxidative stress, which was attenuated by chronic treatment with apocynin to prevent NAD(P)H oxidase activity. The protein expression of the NAD(P)H oxidase subunits NOX2 and p47 phox and overall NAD(P)H oxidase activity were approximately doubled in the cortex of the rats on the high-sodium diet compared with those on the normal sodium intake while both SOD activity and expression were unchanged. By contrast, neither NOX nor SOD protein expression or activity were altered in the medulla when the rats were placed on the high-sodium intake. These data suggest that an elevation in dietary sodium intake can lead to increased generation of reactive oxygen species and a state of oxidative stress in the cortex but not to such a degree that it extends to the medulla. renal cortex; renal medulla; oxidative stress; nicotinamide adenine dinucleotide phosphate oxidase; superoxide dismutase THERE IS NOW A CLEAR consensus that, in many cardiovascular diseases, such as hypertension, heart failure, diabetes, and obesity, a state of oxidative stress exists where there is a raised production of reactive oxygen species that has potentially damaging effects on proteins, lipids, and DNA or react with nitric oxide (NO), thereby removing its functional role in physiological control mechanisms (17,20). Oxidative stress results from an imbalance between the generation of reactive oxygen species, such as superoxide anion (O 2 Ϫ ), hydrogen peroxide, and hydroxyl radical, and the antioxidant defense systems, such as superoxide dismutase (SOD) (18). NAD(P)H oxidases are responsible for the generation of reactive oxygen species, and in unstimulated phagocytes, where it was originally identified, the NAD(P)H oxidase enzyme is composed of gp91 phox , a membrane-integrated catalytic subunit associated with p22 phox , an accessory subunit. The activator (p67 phox ) and the organizer/adaptor subunits (p47 phox and p40 phox ) exist in the cytoplasm and, upon activation, translocate to the membrane to assemble the active oxidase that transfers electrons from the substrate to O 2 , forming O 2 Ϫ . Phagocytic gp91 phox [NAD(P)H oxidase (NOX) 2] has also been detected in vascular, cardiac, renal, and neural cells while its homolog NOX4 is abundant in the kidney and in vascular smooth muscle cells (6, 13). The activ...

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Section: Discussionmentioning

confidence: 99%

“…All rats had access to the diet and tap water ad libitum until 10 -11 wk of age (225-275 g). In two other groups, the tap water contained apocynin, at 2.5 mM, to prevent the binding of NAD(P)H oxidase subunits and thereby decreasing the activity of the enzyme (9,19).…”

Section: Methodsmentioning

confidence: 99%

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Johns

O’Shaughnessy

O'Neill

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…NADPH oxidase has emerged as a major source of oxidative stress in the brain, particularly in neurodegenerative diseases, such as ischemic stroke, Alzheimer's and Parkinson's diseases, HIV dementia, multiple sclerosis, etc (Bedard and Krause, 2007). Recent studies have shown that apocynin placed in the drinking water or in diet are effective at reducing superoxide and oxidative stress in vivo (Cotter and Cameron, 2003;Elmarakby et al, 2005;Hougee et al, 2006;Paliege et al, 2006). No adverse effects were observed with apocynin doses ranging from 2.5 mg/kg/day to 100mg/kg/day and duration between 4 days and 6 weeks (Cotter and Cameron, 2003;Elmarakby et al, 2005;Hougee et al, 2006;Paliege et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that apocynin placed in the drinking water or in diet are effective at reducing superoxide and oxidative stress in vivo (Cotter and Cameron, 2003;Elmarakby et al, 2005;Hougee et al, 2006;Paliege et al, 2006). No adverse effects were observed with apocynin doses ranging from 2.5 mg/kg/day to 100mg/kg/day and duration between 4 days and 6 weeks (Cotter and Cameron, 2003;Elmarakby et al, 2005;Hougee et al, 2006;Paliege et al, 2006). The therapeutic potential of systemic single administration of apocynin has been demonstrated in a dose range of 2.5−12 mg/kg in different animal models (Sonta et al, 2004;Kimura et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of apocynin through its conversion to glycoconjugate but not to diapocynin

et al. 2008

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Apocynin (4-hydroxy-3-methoxyacetophenone) is a major active ingredient from the rhizomes of Picrorhiza kurroa, a botanical plant used as an herbal medicine for treatment of a number of inflammatory diseases. Recently, apocynin is regarded as a specific inhibitor for NADPH oxidase in cell and animal models. In vitro studies indicated conversion of apocynin to diapocynin in the presence of peroxidases, e.g., myloperoxidase, posing the possibility that diapocynin also contributes to the anti-oxidative action of apocynin. The objectives of this study are to examine the bioavailability of apocynin to plasma, liver and brain tissue after intraperitoneal (i.p.) injection, and to examine whether apocynin is converted to diapocynin in vivo. Diapocynin was chemically synthetized and characterized by NMR and IR. Apocynin (5 mg/kg body wt) was injected i.p. to adult male Sprague-Dawley rats and plasma, liver and brain were collected at different times (30 min, 1 h and 2 h) after injection. Samples were treated with β-glucuronidase to hydrolyze the glycosyl linkage and analyzed by HPLC/MS. At 30 min and 1 h after injection, approximately 50% of apocynin was converted to its glycosyl derivative and was distributed in plasma, liver and brain. No diapocynin was detected in any samples. These results indicate rapid glycosylation of apocynin and its transport to blood and other organs but no apparent conversion to diapocynin in vivo.

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“…54 Digoxygenin-labeled UTP and T7 or SP6 RNA polymerase (Roche Applied Science, Mannheim, Germany) were used to generate sense and antisense RNA probes. In situ hybridization was performed as previously described, 55,56 and hybridized RNA probes were visualized using 4-nitroblue tetrazolium chloride. Sections were examined using a Leica DMRB microscope equipped with an interference contrast module (Leica, Wetzlar, Germany).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

Kurt

Paliege

Willam

et al. 2013

Journal of the American Society of Nephrology

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States of low perfusion pressure of the kidney associate with hyperplasia or expansion of renin-producing cells, but it is unknown whether hypoxia-triggered genes contribute to these changes. Here, we stabilized hypoxia-inducible transcription factors (HIFs) in mice by conditionally deleting their negative regulator, Vhl, using the Cre/loxP system with renin-1d promoter-driven Cre expression. Vhl 2/2REN mice were viable and had normal BP. Deletion of Vhl resulted in constitutive accumulation of HIF-2a in afferent arterioles and glomerular cells and HIF-1a in collecting duct cells of the adult kidney. The preglomerular vascular tree developed normally, but far fewer renin-expressing cells were present, with more than 70% of glomeruli not containing renin cells at the typical juxtaglomerular position. Moreover, these mice had an attenuated expansion of renin-producing cells in response to a low-salt diet combined with an ACE inhibitor. However, renin-producing cells of Vhl 2/2REN mice expressed the erythropoietin gene, and they were markedly polycythemic. Taken together, these results suggest that hypoxia-inducible genes, regulated by VHL, are essential for normal development and physiologic adaptation of renin-producing cells. In addition, deletion of Vhl shifts the phenotype of juxtaglomerular cells from a renin-to erythropoietin-secreting cell type, presumably in response to HIF-2 accumulation.

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Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

Cited by 36 publications

References 40 publications

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Bioavailability of apocynin through its conversion to glycoconjugate but not to diapocynin

Deletion of von Hippel–Lindau Protein Converts Renin-Producing Cells into Erythropoietin-Producing Cells

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