Reduced Serum Hydroxyl Radical Scavenging Activity in Erythropoietin Therapy Resistant Renal Anemia

Hirayama, Aki; Nagase, Sohji; Gotoh, Michihiro; Ueda, Atsushi; Ishizu, Tomoko; Yoh, Keigyou; Aoyagi, Kazumasa; Terao, Junji; Kôyama, Akio

doi:10.1080/1071576021000016418

Cited by 20 publications

(18 citation statements)

References 15 publications

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“…In this study we clearly demonstrated that EPO treatment prevents the formation of peroxynitrite. This finding regarding the effects of EPO on free radical production is consistent with the results of previous studies (42)(43)(44).…”

Section: Discussionsupporting

confidence: 93%

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

Cuzzocrea

Mazzon

Paola

et al. 2005

Arthritis & Rheumatism

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Objective. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. The aim of this study was to investigate the effect of EPO on collagen-induced arthritis (CIA) in the mouse.Methods. CIA was induced by intradermal injection of bovine type II collagen (CII) and Freund's complete adjuvant. Starting on day 25, some of the mice with CIA received daily subcutaneous injections of EPO (1,000 units/kg). Two other groups of mice received sham treatment alone or sham treatment followed by EPO treatment, respectively. Arthritis was assessed clinically, radiologically, and histologically. Cytokine and chemokine levels were measured, and neutrophil infiltration into inflamed joints was quantitated. Immunohistochemistry studies were performed to measure protein nitrosylation. Chondrocyte apoptosis was assessed by TUNEL assay.Results. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. Histopathologic features of CIA included erosion of the cartilage at the joint margins. Treatment with EPO starting at the onset of arthritis (day 25) ameliorated the clinical signs on days 26-35 and improved histologic status in the joints and paws. The degree of oxidative and nitrosative damage was significantly reduced in EPO-treated mice as indicated by decreased nitrotyrosine formation and poly(ADP-ribose) polymerase activation. Plasma levels of the proinflammatory cytokine tumor necrosis factor ␣ were also significantly reduced by EPO treatment. In addition, EPO reduced the levels of apoptosis in chondrocytes in articular cartilage, as indicated by decreased TUNEL staining.Conclusion. These findings demonstrate that EPO exerts an antiinflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

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Section: Discussionsupporting

confidence: 93%

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

Cuzzocrea

Mazzon

Paola

et al. 2005

Arthritis & Rheumatism

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“…Indeed, EPO treatment prevented the formation of tissue nitrotyrosine staining in DNBS-treated animals. This result of the effects of EPO on free radical production is in agreement with previous studies (Squadrito et al, 1999;Hirayama et al, 2002). Superoxide and peroxynitrite cause DNA single-strand damage, leading to poly(ADPribose) synthetase activation and cell death (Szabo and Dawson, 1998).…”

Section: Discussionsupporting

confidence: 92%

Erythropoietin Reduces the Development of Experimental Inflammatory Bowel Disease

Cuzzocrea

Mazzon

Paola

et al. 2004

J Pharmacol Exp Ther

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Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) in the colon. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. Here we investigate the effects EPO has on the development of experimental colitis. To address this question, we used an experimental model of colitis induced by dinitrobenzene sulfonic acid (DNBS). When compared with DNBS-treated mice, EPO (1000 IU/kg day s.c.)-treated mice subjected to DNBSinduced colitis experienced significantly lower rates in the extent and severity of the histological signs of colon injury. DNBStreated mice experienced diarrhea and weight loss. At 4 days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as an increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) showed an intense staining in the inflamed colon. On the contrary, the treatment of DNBS-treated mice with EPO significantly reduced the degree of diarrhea and weight loss caused by administration of DNBS. EPO also caused a substantial reduction of the degree of colon injury, the rise in myeloperoxidase activity (mucosa), and the increase in staining (immunohistochemistry) for nitrotyrosine as well as the up-regulation of ICAM-1 caused by DNBS in the colon. Thus, treatment of rat with EPO reduces the degree of colitis caused by DNBS. We propose that EPO may be useful in the treatment of inflammatory bowel disease.

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“…Signal intensities of the hydroxyl radical spin adducts were measured using electron spin resonance (ESR) according to a method previously described [24]. ESR spectra were obtained by JEOL TE-25X ESR equipment (JEOL, Tokyo, Japan) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was used for a spin-trapping reagent.…”

Section: Methodsmentioning

confidence: 99%

Elimination of Lipid Peroxide during Hemodialysis

Obara

Hirayama²,

Gotoh³

et al. 2007

Nephron Clin Pract

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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. The hydroxyl radical scavenging activity was measured for the evaluation of the pro-oxidative side. Results: CE-OOH and PC-OOH were elevated in patients with chronic kidney disease both on and not on HD, while these values were much higher in HD patients. CE-OOH quickly dropped during the first 30 min of HD, then gradually decreased until 240 min. CE-OOH concentrations were related to those of apoA-I. In contrast, PC-OOH showed an increase 30 min after the start of HD, a change which resembled that of LCAT and was the reverse of the hydroxyl radical scavenging activity. Conclusion: These results demonstrate the antioxidative action through CE-OOH elimination involving apoA-I. The pro- and antioxidative effects of HD on LOOH are not uniform but PC-OOH is mainly influenced prooxidatively.

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Reduced Serum Hydroxyl Radical Scavenging Activity in Erythropoietin Therapy Resistant Renal Anemia

Cited by 20 publications

References 15 publications

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

Erythropoietin Reduces the Development of Experimental Inflammatory Bowel Disease

Elimination of Lipid Peroxide during Hemodialysis

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