Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats

Nakamura, Kazuo; Kojima, Kenichiro; Arai, Takami; Shirai, Masaki; Usutani, Saburo; Akimoto, H; Masaoka, Hiroyuki; Nagase, Mitsumasa; Yamamoto, Masahide

doi:10.1046/j.1365-2362.1998.00378.x

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…Increased lipid peroxidation has also been measured in glomeruli from humans with congenital nephrotic syndrome of the Finnish type [32]. Further evidence in support of this potential mechanism includes studies demonstrating that treatments commonly used to treat nephrotic syndrome in humans, such as glucocorticoids and other immunosuppressants, can increase glomerular AOE and protect against PAN-induced injury [12,14], studies showing that AOE or antioxidants can ameliorate the effects of PAN [28,29,33,34] and that inhibition of AOE exacerbates PAN nephrosis [35]. A metabolite of PAN has also previously been shown to be converted by glomeruli to hypoxanthine, a component of the xanthine/hypoxanthine pathway for the production of superoxide radicals [36].…”

Section: Discussionmentioning

confidence: 99%

Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin aminonucleoside

Vega-Warner¹,

Ransom²,

Vincent³

et al. 2004

Kidney International

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These results demonstrate that (1) PAN treatment induces significant early changes in podocyte ROS, (2) podocytes can mount an antioxidant defense against oxidant stress, and (3) this protective response is initiated prior to the development of extensive oxidant-induced podocyte structural injury. These findings suggest that enhancement of podocyte AOE activities represent a potential therapeutic target to protect from or ameliorate podocyte injury during nephrotic syndrome.

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Section: Discussionmentioning

confidence: 99%

Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin aminonucleoside

Vega-Warner¹,

Ransom²,

Vincent³

et al. 2004

Kidney International

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“…The results of these studies suggest the involvement of reactive oxygen species (ROS), such as superoxide or hydroxyl radicals, in the disease pathogenesis [1,2,3,4,5,6,7,8,9,10]. Isolated glomeruli from these rats show increases in luminol-amplified chemiluminescence [1,2] and elevated malondialdehyde levels [3,4,5,6,7]. Chaverri et al [3] reported that the nephrotic syndrome induced by PAN was ameliorated by a-tocopherol supplementation.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress in a rat model of nephrosis can be quantified by electron spin resonance

Nakakura

Ashida

Hirano

et al. 2004

Pediatric Nephrology

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The pathogenesis of nephrotic syndrome is not clear. In this study, we used electron spin resonance (ESR) to evaluate levels of reactive oxygen species in rats with puromycin aminonucleoside (PAN)-induced nephrosis. Twenty-six Wistar rats were divided into four groups: (1) PAN treated, (2) PAN treated and alpha-tocopherol supplemented, (3) supplemented with alpha-tocopherol only, (4) control. On day 9, urinary protein excretion was measured. On day 10, all animals were sacrificed with retrograde perfusion via the aorta to obtain renal venous perfusates. The signal intensities of ascorbate radicals in the perfusates were determined by ESR. After perfusion, the kidneys were isolated and sieved to obtain glomeruli for determination of glomerular thiobarbituric acid-reactive substance (TBArs) and alpha-tocopherol. Urinary protein excretion by PAN-treated rats increased significantly on day 9 and was reduced by alpha-tocopherol supplementation. The ascorbate radical intensity and glomerular TBArs level were higher in PAN-treated than in control rats and were both suppressed to control levels by alpha-tocopherol supplementation. There were positive correlations between ascorbate radical intensity and the daily urinary protein, as well as between ascorbate radical intensity and the glomerular TBArs level. Hence, it is possible to quantify oxidative stress due to PAN nephrosis by ESR. Our findings suggest that lipid peroxidation plays an important role in the pathogenesis of proteinuria in PAN-treated rats.

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“…Furthermore, podocytes receiving SPE, SalB, RA and TAC had lower ROS production than the PAN group. It has been known that ROS is one of the major pathogenic causes of oxidative stress in PAN nephrosis, and the glomerular injury is acutely mediated by the overproduction of ROS [4], which then may interact with biomolecules, including DNA, resulting in potentially deleterious cellular consequences [6]. A large number of signaling pathways appear to be regulated by ROS, particularly with regard to the regulation of differentiation, apoptosis and proliferation [30].…”

Section: Discussionmentioning

confidence: 99%

“…In vivo studies have demonstrated that PAN-induced glomerular injury is acutely mediated via the overproduction of reactive oxygen species (ROS) [4,5]. …”

Section: Introductionmentioning

confidence: 99%

Antioxidative Stress Effects of <b><i>Salvia przewalskii</i></b> Extract in Experimentally Injured Podocytes

Liu

Liu²,

Yang³

et al. 2016

Nephron

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Background: Oxidative stress is a leading cause of puromycin aminonucleoside (PAN)-induced nephrosis. As the inhibition of oxidative stress may improve injury of podocyte, we aimed at examining the effect of total phenolic acid extract of Salvia przewalskii (SPE) on PAN-induced oxidative stress in vivo and in vitro. Methods: Seventy-two male Sprague-Dawley rats were randomly assigned into 6 groups (n = 12), PAN alone, tacrolimus (TAC), SPE (50, 100 and 200 mg/kg) and normal control group. Salvianolic acid B (SalB, 5.52%) and rosmarinic acid (RA, 31.58%) were isolated from SPE. The intensities of 8-oxo-2'-deoxyguanosine (8-OHdG) were evaluated by immunofluorescence. In vitro, the podocytes were assigned into groups of control, PAN alone, TAC (1 μg/ml), SPE (158, 316 μg/ml), SalB (8.5, 17 μg/ml) and RA (25, 50 μg/ml). The intracellular reactive oxygen species (ROS) production and cell apoptosis rate were measured by flow cytometry. Form factor and aspect ratio were calculated to assess mitochondrial morphology. Results: In vivo, PAN increased the intensity of 8-OHdG in the renal tissue in the PAN group (p < 0.05). The high-dose SPE reduced 8-OHdG significantly at levels comparable to TAC alone (p > 0.05) on day 15. The intracellular ROS production, podocytes apoptosis rate and mitochondrial fragmentation increased significantly following PAN exposure in podocytes (p < 0.05). Treatment with high-dose SalB significantly ameliorated the increase in the expression of ROS and revised the structure of mitochondria. The percentage of apoptotic cells was decreased compared with the PAN group after SPE, SalB, RA, and TAC treatment for 24 h (p < 0.05). Conclusion: These findings suggest that high-dose SPE significantly attenuated 8-OHdG in PAN nephrosis. Antioxidative stress effects of high-dose SPE, SalB against PAN-stimulated cultured podocyte via mechanisms include suppression of ROS expression and mitochondria fission. In addition, SPE, SalB and RA can suppress PAN-induced apoptosis.

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Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats

Abstract: DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.

Cited by 16 publications

References 32 publications

Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin aminonucleoside

Induction of antioxidant enzymes in murine podocytes precedes injury by puromycin aminonucleoside

Oxidative stress in a rat model of nephrosis can be quantified by electron spin resonance

Antioxidative Stress Effects of <b><i>Salvia przewalskii</i></b> Extract in Experimentally Injured Podocytes

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