Verapamil Prevents Impairment in Filterability of Human Erythrocytes Exposed to Oxidative Stress

Okamoto, Ken‐ichi; Maruyama, Toru; Kaji, Yuichi; Harada, Mine; Shiro, Motoo; Fujino, Takehiko; Uyesaka, Nobuhiro

doi:10.2170/jjphysiol.54.39

Cited by 30 publications

(27 citation statements)

References 35 publications

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“…It is well known that the formation of met-Hb generates various reactive oxygen species, such as the superoxide anion (O 2 -), hydrogen peroxide (H 2 O 2 ), and hydroxyradical [20,21]; accordingly, these reactive oxygen species exert further oxidative stress on intact erythrocytes and facilitate additional impairment of their membranes. In fact, we confirmed that several kinds of oxidative stresses remarkably impair erythrocyte filterability, using O 2 - [22], phenylhidrazine [10], and tert-butyl hydroperoxide (tBHP) [23]. Thus it is very likely that the marked decrease in filterability induced by the combination therapy (Figs.…”

Section: Discussionsupporting

confidence: 69%

Impaired Filterability of Erythrocytes from Patients with Chronic Hepatitis C and Effects of Eicosapentaenoic Acid on the Filterability

et al. 2007

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Abstract:Although erythrocyte filterability plays a key role in microcirculation, it is unknown whether the filterability of erythrocytes from patients with chronic hepatitis C (CH-C) is impaired. This study aimed to investigate erythrocyte filterability in CH-C patients in relation to medical treatment. The mean erythrocyte filterability (%) for all 24 patients with CH-C (69.2 ± 10.8%) was significantly lower than that for 5 normal controls (80.5 ± 1.7%, P < 0.03). In 8 patients, the combination therapy of ribavirin (RBV) and interferon improved liver function but caused anemia. The filterability after treatment (57.8 ± 12.8%) was lower than that before treatment (70.8 ± 9.7%, P < 0.05). Decreased filterability showed no correlation with the mean corpuscular volume or mean corpuscular Hb concentration during treatment, suggesting that the decrease in filterability mainly arises from changes in erythrocyte membrane properties. We investigated the protective effects of eicosapentaenoic acid (EPA) on the RBV-induced anemia. Filterability in 7 responders was markedly improved from 68.4 ± 4.6% to 77.4 ± 2.4% (P < 0.001), but not in 3 nonresponders. In the responders, the progression of anemia was restrained. In conclusion, we found an obvious impairment of the filterability of erythrocytes from CH-C patients, further impairment of the filterability induced by oxidative membrane damage caused by RBV leading to hemolytic anemia, and amelioration of the filterability caused by the antioxidative effects of EPA.Key words: chronic hepatitis, erythrocytes, filterability, eicosapentaenoic acid (EPA), oxidative stress.Hepatitis C virus (HCV) causes one of the most common and serious infections in Japan, affecting almost two million Japanese at present. Approximately 80% of patients with acute HCV infection will subsequently develop chronic infection, and an estimated 20% to 30% will develop cirrhosis and hepatocellular carcinoma [1]. The most effective treatment for chronic hepatitis C (CH-C) is antiviral combination therapy with interferon (IFN) and ribavirin (RBV) [2]. RBV is a water-soluble synthetic guanosine analog that exerts antiviral activity against DNA and RNA viruses after intracellular phosphorylation [3]. Current studies indicate that combination therapy with IFN and RBV (IFN/RBV) is associated with higher rates of sustained virological, biochemical, and histological responses compared to IFN monotherapy [4]. However, one of the major adverse effects of the combination therapy is RBV-induced hemolytic anemia; 67% of treated patients developed anemia [5]. This adverse effect has been ascribed to the accumulation of RBV triphosphate in erythrocytes, which leads to their oxidative injury [5,6]. It is therefore suspected that the hemolytic anemia stems from impaired erythrocyte deformability. However, there is little data available on the deformability of erythrocytes in patients with CH-C, as well as for the patients treated with IFN/RBV.The deformability of erythrocytes that pass through the microvascular network ...

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Section: Discussionsupporting

confidence: 69%

Impaired Filterability of Erythrocytes from Patients with Chronic Hepatitis C and Effects of Eicosapentaenoic Acid on the Filterability

et al. 2007

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“…It is controversial concerning whether diminished erythrocyte membrane plasmalogen is the cause or the result of severe atherosclerosis requiring endovascular therapy. Acute peroxidation of human erythrocytes exposed to tertial butyl-hydroperoxide (tBHP) causes formation of methemoglobin, erythrocyte membrane protein degradation, phospholipid peroxidation and selective reduction of erythrocyte membrane pl-PE (from 14.5 0.5 to 11.3 0.2%) in the same HPLC method as in this study 6,10) . These results strongly support that pl-PE is consumed as an endogenous antioxidant defense for any acute or persistent oxidative damages, because lyso-ethanolamine plasmalogen, a product of acid hydrolysis of pl-PE, could not be detected by our erythrocyte lipid extraction method using hexane/isopropanol mixture 10) .…”

Section: Erythrocyte Membrane Plasmalogenmentioning

confidence: 88%

【Original Contribution】 Plasma and Erythrocyte Membrane Plasmalogen Diminished in Severe Atherosclerotic Patients Undergoing Endovascular Therapy

et al. 2017

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“…The absorption peak of another part was read at 630 nm in the presence of 5% potassium ferricyanide and then read again at 630 nm after the addition of 5% potassium cyanide. The formation of methemoglobin (met-Hb, %) was calculated as previously reported 11) .…”

Section: Methemoglobin Assaymentioning

confidence: 99%

【Original Contribution】 Marked Impairment of Human Erythrocyte Filterability Caused by Oxidant Stress with AAPH Precedes Oxidative Hemolysis

et al. 2014

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Verapamil Prevents Impairment in Filterability of Human Erythrocytes Exposed to Oxidative Stress

Cited by 30 publications

References 35 publications

Impaired Filterability of Erythrocytes from Patients with Chronic Hepatitis C and Effects of Eicosapentaenoic Acid on the Filterability

Impaired Filterability of Erythrocytes from Patients with Chronic Hepatitis C and Effects of Eicosapentaenoic Acid on the Filterability

【Original Contribution】 Plasma and Erythrocyte Membrane Plasmalogen Diminished in Severe Atherosclerotic Patients Undergoing Endovascular Therapy

【Original Contribution】 Marked Impairment of Human Erythrocyte Filterability Caused by Oxidant Stress with AAPH Precedes Oxidative Hemolysis

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