Spherical carbon adsorbent (AST-120) protects deterioration of renal function in chronic kidney disease rats through inhibition of reactive oxygen species production from mitochondria and reduction of serum lipid peroxidation.

Background/aim: An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats.

Methods: CKD was induced by 5/6 nephrectomy.

In vivo imaging of renal redox status during azelnidipine treatment.

The effect of the calcium channel blocker azelnidipine on the redox status of a murine hypertension model was analyzed and imaged using in vivo low frequency electron paramagnetic resonance (EPR). A murine two kidney-one clip (2K1C) hypertension model was produced by a clipping of the right renal artery. The resulting hypertensive mice were treated with low-dose azelnidipine (1 mg/kg/d), with high-dose azelnidipine (3 mg/kg/d) or without azelnidipine (HT group).

Nitric oxide protection against adriamycin-induced tubulointerstitial injury.

It is well known that oxidative stress is related to the pathogenesis of adriamycin (ADR) nephropathy. However, it is unclear how nitric oxide (NO) is associated with the pathophysiological process after ADR administration. The NO level in a kidney homogenate was assayed by electron paramagnetic resonance (EPR) spectrometry using a direct in vivo NO trapping technique after ADR administration.

Effect of CV159-Ca(2+)/calmodulin blockade on redox status hepatic ischemia-reperfusion injury in mice evaluated by a newly developed in vivo EPR imaging technique.

1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester (CV159) exhibits selective blocking of Ca(2+)/calmodulin and inhibits Ca(2+) overloading in living organisms. The effects of this antagonist in mice with hepatic ischemia-reperfusion injury were investigated using electron paramagnetic resonance imaging (EPRI) and ex vivo EPR (x-band EPR) techniques. The EPRI determined that the 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl half-life in CV159-treated mice was significantly shorter than that in untreated mice and was almost equal to that in the sham group.

Proanthocyanidin promotes free radical-scavenging activity in muscle tissues and plasma.

The present study was carried out to clarify the effect of oral administration of proanthocyanidin (PA) on radical-scavenging activity in muscle and plasma using electron spin resonance (ESR). Eight-week-old male Wistar rats were orally administered with 3 doses per day of 1 mL of 0.05% (PA0.

Elimination of lipid peroxide during hemodialysis.

Background/aims: This study is aimed to show the antioxidative effect of hemodialysis (HD) by demonstrating the elimination of toxic lipid peroxides.

Methods: Blood samples were obtained from patients on regular maintenance HD before and 15, 30, 60, 120 and 240 min after the start of each HD session. Plasma cholesteryl ester hydroperoxide (CE-OOH), phosphatidylcholine hydroperoxide (PC-OOH), and eliminators of lipid peroxides (LOOH) such as apolipoprotein A-I (apoA-I) and lecithin:cholesterol acyltransferase (LCAT) were investigated.

In vivo detection of intrinsic reactive oxygen species using acyl-protected hydroxylamine in puromycin nephrosis.

Intrinsic reactive oxygen species (ROS) in a rat model of human minimal change nephropathy were detected directly using an in vivo electron paramagnetic resonance (EPR) method with 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP) in real time. The nephrosis was induced by the intravenous administration of 75 mg/kg of puromycin aminonucleoside (PAN). It was found that ROS in the kidney were increased 1 h after the administration of PAN.

Electron paramagnetic resonance imaging of oxidative stress in renal disease.

The importance of analyzing the kinetics of reactive oxygen species or related substances in vivo is increasing. Electron paramagnetic resonance (EPR) is currently a powerful method for in vivo, non-invasive analysis of oxidative stress. We have applied EPR imaging for murine renal ischemia-reperfusion injury, as a model of acute renal damage, and NF-E2-related factor 2 (Nrf2)-deficient mice, a model for chronic progressive renal disease.

Normalizing renal reducing ability prevents adriamycin-induced proteinuria.

Reactive oxygen species play an important role in adriamycin (ADR) nephropathy. We showed by in vivo electron paramagnetic resonance (EPR) that renal reducing ability (RRA) declined on the 7th day after ADR administration. Proteinuria appeared after the decline in RRA.

Evaluation of adriamycin nephropathy by an in vivo electron paramagnetic resonance.

A rat model for human minimal change nephropathy was obtained by the intravenous injection of adriamycin (ADR) at 5 mg/kg. By using an in vivo electron paramagnetic resonance (EPR) spectrometer operating at 700 MHz, the temporal changes in signal intensities of a nitroxide radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), in the kidneys of rats with ADR nephropathy were investigated. The decay rate of the EPR signal intensity obtained in the kidney is indicative of the renal reducing ability.

Erythropoietin-resistant anaemia in a predialysis patient with Klinefelter syndrome.

A diabetic predialysis patient who had significantly reduced sensitivity to erythropoietin therapy was admitted to Tsukuba University Hospital. Many factors that might have been the cause of the erythropoietin resistance were examined, and a diagnosis of refractory anaemia was made based on a bone marrow aspiration biopsy. A cytogenetic abnormality (47, XXY) was also detected in the bone marrow biopsy specimen, and hence the patient was also diagnosed with Klinefelter syndrome.

Management of unruptured cerebral aneurysms in patients with polycystic kidney disease.

Background: Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder characterized by bilateral multiple renal cysts and early onset chronic renal failure. PKD patients tend to suffer their subarachnoid hemorrhage at a younger age. Unruptured aneurysms in PKD patients are not always innocuous, and proactive treatment has been indicated for these lesions.

In vivo imaging of oxidative stress in ischemia-reperfusion renal injury using electron paramagnetic resonance.

Oxidative stress during ischemia-reperfusion acute renal failure (IR-ARF) was noninvasively evaluated with in vivo electron paramagnetic resonance (EPR) imaging. Female ICR mice underwent left nephrectomy and 30-min ischemia-reperfusion of the right kidney. Oxidative stress was evaluated as organ reducing activity with the half-lives of the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) using 1) conventional L-band EPR, which showed organ-reducing activity in the whole abdominal area; and 2) EPR imaging, which showed semiquantitative but organ-specific reducing activity.

Treatment with the purine synthesis inhibitor mizoribine for ANCA-associated renal vasculitis.

Background: The common treatment for antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis is oral cyclophosphamide (CYC)-corticosteroid combination therapy. However, there are serious complications associated with long-term use of CYC. In this study, we investigate the efficacy of a purine synthesis inhibitor, mizoribine, for patients at high risk for relapse.

Stimulatory effect of IGF-I and VEGF on eNOS message, protein expression, eNOS phosphorylation and nitric oxide production in rat glomeruli, and the involvement of PI3-K signaling pathway.

Nitric oxide (NO) is reported to be involved in the pathogenesis of renal hyperfiltration in the early stage of diabetic nephropathy. We set out to determine whether IGF-I and/or VEGF165 directly stimulate NO production in rat glomeruli and whether the expression of NO synthase (NOS) isoforms as well as eNOS phosphorylation contribute to NO generation by IGF-I and VEGF. Long-term exposure to IGF-I and/or VEGF165 augments NO production through increased eNOS mRNA, protein expression and phosphatidylinositol 3-kinase (PI3-K) signaling pathway plays a major role in this process; short-term exposure to IGF-I and/or VEGF(165) activates eNOS activity via phosphorylation by a PI3-K/Akt dependent pathway.

Oxidative stress during leukocyte absorption apheresis.

Leukocyte absorption apheresis absorbs leukocytes to the apheresis columns involving leukocyte activation. This process is regarded as bioincompatible and avoided in hemodialysis or other extracorporeal circulation processes. Thus, leukocyte apheresis has a potential risk to exacerbate in vivo oxidative stress.

Stable nitroxide Tempol ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischemia.

Oxygen free radicals have been implicated in the pathogenesis of cerebral ischemia and reperfusion injury. 4-Hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (Tempol) has been reported as a stable nitroxide and a membrane-permeable free radical scavenger. This study was performed to investigate the mechanism of Tempol in attenuating ischemia-reperfusion injury in a rat model of transient focal cerebral ischemia.

Prevention of delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

The delayed cerebral vasoconstriction known as cerebral vasospasm remains a significant cause of permanent neurological deficit and death following aneurysmal subarachnoid hemorrhage despite the best current medical therapies. The mechanism of cerebral vasospasm remains unknown. Several new drugs have been tested in animal models of subarachnoid hemorrhage, and these experimental studies have contributed to a better understanding of the potential mechanisms that lead to cerebral vasospasm.

EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice.

Mice that lack the Nrf2 (NF-E2-related factor 2) transcription factor develop a lupus-like autoimmune nephritis. The tissue-reducing activity of Nrf2-deficient mice was evaluated using a combination of real-time EPR imaging and spin probe kinetic analysis. Substantial delay in the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL) disappearance in the liver and kidneys of Nrf2-deficient mice was observed by EPR imaging.

Importance of renal mitochondria in the reduction of TEMPOL, a nitroxide radical.

Spin probing methods using an electron spin resonance (ESR) spectrometer are used extensively and bring us a lot of information about in vivo redox mechanisms. However, the in vivo reducing mechanisms of exogenous nitroxide radicals, which serve as typical spin probing reagents are not clear. To clarify this, we examined the sequential kinetics of a spin probe, 4-hydroxy 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) in the in vivo organs, tissue homogenates and subcellular fractions of kidney and liver using an in vivo and X-band ESR spectrometers.

Association of ecNOS gene polymorphisms with end stage renal diseases.

Nitric oxide (NO) is a very potent regulator of intrarenal hemodynamics and is thought to be an important factor in the deterioration of renal function. Several polymorphisms of the endothelial NO synthase (eNOS) gene have been reported. For instance, tandem 27-bp repeats in intron 4 of the eNOS gene are polymorphic, i.

Electron paramagnetic resonance imaging of nitric oxide organ distribution in lipopolysuccaride treated mice.

The recent development of electron paramagnetic resonance (EPR) permits its application for in vivo studies of nitric oxide (NO). In this study, we tried to obtain 3D EPR images of endogenous NO in the abdominal organs of lipopolysuccaride (LPS) treated mice. Male ICR mice, each weighing about 30 g, received 10 mg/kg of LPS intraperitoneally.

Inhibition by heparin of protein kinase C activation and hydroxyl radical generation in puromycin aminonucleoside treated isolated rat hepatocytes.

Heparin has been reported to have many actions similar to calcium-dependent protein kinase (PKC) inhibitors. We have found that puromycin aminonucleoside (PAN) increases hydroxyl radical generation and this was prevented by H-7, a PKC inhibitor in isolated rat hepatocytes. In this study, we investigate the effect of heparin on the increased hydroxyl radical generation as well as PKC activation by PAN in isolated rat hepatocytes.