Effects of Glutathione Depletion on Hypoxia-induced Erythropoietin Production in Rats

Ando, Daisuke; Yamakita, Mitsuya; Yamagata, Zentaro; Koyama, Katsuhiro

doi:10.2114/jpa2.28.211

Cited by 3 publications

(3 citation statements)

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“…Taking together all the studies, the role of ROS and intracellular redox homeostasis on the HIF1-regulation remains controversial. In a recent in vivo study in rats, Ando et al (2009) showed that the signiWcant increase in EPO concentrations after an acute hypoxic stimulus was not modiWed by a pharmacological inhibition of glutathione synthesis. This raises questions about the central role of cellular redox changes in the hypoxia-induced EPO secretion.…”

Section: Discussionmentioning

confidence: 99%

Effect of N-acetyl-cysteine and hyperoxia on erythropoietin production

et al. 2011

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Previous studies in healthy subjects have shown an increase in erythropoietin (EPO) production after administration of N-acetyl-cysteine (NAC). These authors hypothesized that NAC increases intracellular reduced glutathione, decreasing reactive oxygen species and enabling EPO production. We investigated if EPO production could be stimulated with a single dose of NAC, after 90 min of pure oxygen breathing. Thirty-eight healthy volunteers were randomized into either the control (C) group or the NAC group, which received 600 mg NAC PO dissolved in a glass of orange juice, 60 min before breathing 15 L/min of 100% normobaric oxygen. Orange juice was administered to both groups. Blood samples for EPO measurement were taken at T0, before the orange juice administration, and T1, T2, T3 and T4, respectively, 8, 24, 32 and 48 h after the orange juice. The EPO concentrations of the NAC group decreased significantly at T1, followed by a significant increase compared to baseline, which was obvious until T4. The EPO concentrations of the C group did not show any significant variations. In this study, a significant increase of EPO production was observed after a short-term hyperoxic stimulus only when preceded with the administration of a single dose of NAC.

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Section: Discussionmentioning

confidence: 99%

Effect of N-acetyl-cysteine and hyperoxia on erythropoietin production

et al. 2011

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“…The Withanolide A feeding to rats was done for 21 days prior to and during exposure to hypobaric hypoxia for 7 days. Buthionine sulfoximine (4 mM/kg BW) was dissolved in phosphate buffer saline to a volume of 1 ml and administrered intraperitoneally (i.p) [27] . Metyrapone (50 mg/kg BW) was dissolved in the 40% polyethylene glycol (PEG) (w/v) in physiological saline.…”

Section: Methodsmentioning

confidence: 99%

Withanolide A Prevents Neurodegeneration by Modulating Hippocampal Glutathione Biosynthesis during Hypoxia

et al. 2014

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Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)–related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner.

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“…Treating chronic renal failure with exogenous reductive glutathione can improve the reduction of red blood cells, reduce the concentration of oxidized glutathione, decrease the ratio of oxidized/reduced glutathione, stabilize the red blood cell membrane, and prolong the life of the red blood cell [22]. Research has shown that the effects of supplemental reductive glutathione on anemia are remarkable than only use erythropoietin [23].…”

Section: Reduced Glutathionementioning

confidence: 99%