Effect of Olmesartan on Oxidative Stress in Hemodialysis Patients

Kadowaki, Daisuke; Anraku, Makoto; Tasaki, Yuka; Kitamura, Kenichiro; Wakamatsu, Shiho; Tomita, Kimio; Gebicki, Janusz M.; Maruyama, Toru; Otagiri, Masaki

doi:10.1291/hypres.30.395

Cited by 38 publications

(30 citation statements)

References 40 publications

(46 reference statements)

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“…[16][17][18][19] We previously reported that olmesartan exhibited antioxidant activity in HD patients, even though it was used as a clinical dose for the first time. 6) From the findings of this clinical study, it is also possible that the antioxidant properties of olmesartan are independent of its antihypertensive activity. Therefore, we examined the issue of whether or not the antioxidant properties of olmesartan are related to its phar- macological activity, such as blood lowering effect and renoprotective action using CRF model rats.…”

Section: Discussionmentioning

confidence: 86%

“…These phenomena were very similar to the results obtained from a clinical study involving HD patients. 6) For example, in both CRF rats and HD patients, the oxidized albumin ratio was significantly decreased at 4 weeks by the administration of olmesartan (Fig. 2).…”

Section: Discussionmentioning

confidence: 88%

“…For example, we previously reported on the radical scavenging activity of olmesartan based on the inhibition of the generation of albumin hydroperoxides via g-irradiated hydroxyl radicals and the auto oxidation of albumin. 6) Moreover, Miyata et al reported that olmesartan suppresses the Fenton reaction by chelating metals and the production of carbon center radicals or hydroxyl radicals. 5) Very recently, Naya et al reported that olmesartan exerts the antioxidant effects by inducing SOD activity in blood vessels, and this effect might be related to the protection of vascular endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…8) Analysis of Oxidized Albumin Ratio by HPLC Highperformance liquid chromatography (HPLC) was used to analyze serum albumin, as described previously. 6,8,9) Serum samples were immediately frozen and stored at Ϫ80°C until used for analysis. Typically, 5 ml aliquots of serum were analyzed on a Shodex Asahipak ES-502N column (Showa Denko Co., Ltd., Tokyo, Japan).…”

Section: Evaluation For Antioxidant and Renoprotective Activity Of Olmentioning

confidence: 99%

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Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

Kadowaki

Anraku

Tasaki

et al. 2009

Biological & Pharmaceutical Bulletin

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The renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). It has recently been revealed that the elevated levels of RAS are associated with various organ impairments. Thus, an angiotensin II receptor blocker (ARB) and an angiotensin converting enzyme inhibitor (ACEI) are effective for treating hypertension and show protective effects for the heart or kidney. For example, in a clinical trial in which the effect of ARB valsartan and calcium channel blocker (CCB) amlodipine were compared in patients with diabetes, valsartan was found to decrease the urinary albumin excretion rate to a greater extent than CCB, while BP was reduced to the same level.1) Consequently, RAS antagonists may exert a renal protective effect that is independent of its antihypertensive effect, and may be involved in reducing of the levels of oxidative stress. In fact, contrary to CCB, ARB improved endothelium-dependent coronary dilation in hypertensive patients independent of BP reduction. These beneficial effects on coronary vasomotion might be a result of the antioxidant properties of ARBs. 2)Olmesartan medoxomil, a prodrug that is converted into the active metabolite olmesartan has recently been developed in association with ARB.3,4) Miyata et al. reported that the antioxidant effects of olmesartan were greater than any other ARBs in an in vitro study. 5) We recently reported, in an in vitro study, that clinical concentrations of olmesartan exert antioxidant properties. This was further confirmed in a clinical trial for hemodialysis (HD) patients as well.6) We also reported that the antioxidant effects of olmesartan might be independent of its BP lowering ability. To develop a better understanding of the antioxidant effect of olmesartan in vivo, relationships between the antioxidant activity of olmesartan and pharmacological effects, such as renoprotective or BP lowering effects, were examined using the 5/6 nephrectomy rat. MATERIALS AND METHODS MaterialsOlmesartan was obtained from the DaiichiSankyo Pharmaceutical Co., Ltd. (Tokyo, Japan). All other chemicals were of the highest grade available from commercial sources.Animals and Treatment Male Wister rats were purchased from Seac Yoshitomi, Ltd. (Fukuoka, Japan). The experimental protocol was inspected and approved by the Animal Care and Use Committee of School of Medicine, Kumamoto University and the law and notification of the Japanese government prior to commencement of the study. Fiveweek-old male rats weighing 140-150 g were subjected to a 5/6 nephrectomy, as previously described. 7,8) Six weeks after the operation, the treated rats showed increased plasma concentrations of creatinine (Ͼ1.0 mg/dl), and reduced levels of creatinine clearance (1.12 approximately 1.24 ml/min). Agematched Sham-operated rats were used for comparison. These rats were divided into three groups as follows: (a) untreated nephrectomized group (nϭ4-6). (b) Olmesartan (10 mg/kg/d) treated nephrectomized group (nϭ4-6). (c) Sham-operated rats (nϭ4-6). All of the rats received s...

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Evaluation For Antioxidant and Renoprotective Activity Of Olmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

Kadowaki

Anraku

Tasaki

et al. 2009

Biological & Pharmaceutical Bulletin

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“…[16][17][18] Serum samples were immediately frozen and stored at Ϫ80°C until used for analysis. From the HPLC profile, the content of each albumin fraction (rat mercaptalbumin, f[RMA]; rat nonmercaptalbumin, f[RNA]) was estimated as the area of the RNA fraction divided by the RMA fraction of the serum albumin peak.…”

Section: Methodsmentioning

confidence: 99%

The Antioxidative and Antilipidemic Effects of Different Molecular Weight Chitosans in Metabolic Syndrome Model Rats

Anraku

Michihara

Yasufuku

et al. 2010

Biological & Pharmaceutical Bulletin

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The metabolic syndrome is a constellation of risk factors, including atherogenic dyslipidemia, impaired fasting glucose, hypertension, and central adiposity, predisposing to higher risks of oxidative stress, type 2 diabetes and atherosclerotic cardiovascular disease. [1][2][3][4] In particular, an enhancement in oxidative stress by reactive oxygen species (ROS) has been proposed as a common pathomechanism by which cardiovascular risk factors affect the vessel wall to induce and amplify vessel and organ injury. Thus, an appropriate evaluation and reduction in oxidative stress in the circulating blood is important from the viewpoint of protecting vascular endothelium and vascular smooth muscle cells against oxidative stress.5-7) Dietary modifications, which include the use of antilipidemic supplements, are one of the key elements in the management of these metabolic abnormalities. For example, chitosan has been proposed as a safe and efficacious dietary supplement that can contribute to weight loss by reducing the amount of dietary fat absorbed, thereby improving calorie balance. 8)Chitosan, a cationic polysaccharide produced by the Ndeacetylation of chitin under alkaline conditions, contains a linear sugar backbone, composed of b-1,4-linked glucosamine units. It exhibits a wide variety of biological activities except for cholesterol-lowering effects.9-11) A property of particular interest for this study is the antioxidant properties of chitosan. Santhosh et al. reported that the administration of chitosan to rats that had been treated with isoniazid or rifampicin inhibited the oxidation of hepatotoxic lipids.12) It had also been reported that chitosan, when injected, inhibited glycerol-induced renal oxidative damage in rats.13) Because of the numerous in vitro and in vivo antioxidant studies that have appeared, chitosan has attracted considerable attention from researchers. In spite of this, however, relationships between molecular weight (MW) and antioxidant activity have not been extensively investigated in in vivo studies.In this study, we examined the effect of high and low MW chitosan supplements (HMC; 1000 kDa and LMC; 30 kDa) on oxidative stress in normal and metabolic syndrome model rats, in an attempt to better understand the potential role for HMC and LMC as an antioxidant in the systemic circulation. Oxidative stress was evaluated by monitoring oxidized serum albumin levels, a sensitive marker for protein oxidation, in the systemic circulation.14,15) We also investigated the role of HMC and LMC as a chelator, to develop a better understanding of the mechanism of the antioxidant activity of HMC and LMC in metabolic syndrome model rats. MATERIALS AND METHODSMaterials LMC (MWϭ30 kDa) and HMC (MWϭ1000 kDa) were obtained from Nippon Kayaku Food Techno Co., Ltd. (Gunma, Japan). All other chemicals were of the highest grade available and were obtained from commercial sources.Animals and Treatment Male (6 weeks old) Wistar Kyoto rats as a normal model (Normal-rats) and spontaneously hypertensive rat/ND mcr-cp ...

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A fresh look at interferon-α signaling and treatment outcomes in chronic hepatitis C

Bellecave

Moradpour

2008

Hepatology

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Effect of Olmesartan on Oxidative Stress in Hemodialysis Patients

Abstract: The effect of olmesartan, an inverse angiotensin II type 1 receptor blocker (ARB), on oxidative stress in hemodialysis (HD) patients is not fully understood, and has not been widely investigated in vitro or in vivo.

Cited by 38 publications

References 40 publications

Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

Evaluation for Antioxidant and Renoprotective Activity of Olmesartan Using Nephrectomy Rats

The Antioxidative and Antilipidemic Effects of Different Molecular Weight Chitosans in Metabolic Syndrome Model Rats

A fresh look at interferon-α signaling and treatment outcomes in chronic hepatitis C

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