Effect of ascorbic acid administration in hemodialysis patients on in vitro oxidative stress parameters: Influence of serum ferritin levels

Wei Teing Chen, Yuh Feng Lin, Fu Chiu Yu, Woei Yau Kao, Wen Hsin Huang, Horng Chin Yan

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Ascorbic acid supplementation has been recommended to circumvent resistance to erythropoietin, which sometimes occurs in iron-overloaded uremic patients. In considering the pro-oxidant effect of ascorbic acid, the authors hypothesize that adjuvant therapy with larger doses of ascorbic acid in hemodialysis patients with iron overload may raise the risk of increasing free radical generation. The oxidative stress of intravenous ascorbic acid supplementation in hemodialysis patients was evaluated in this study. Methods: Six healthy subjects and 29 hemodialysis patients were enrolled. Chemical scavenging activity of various compounds was measured by in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Free radical generation was determined in vitro by lucigenin-enhanced chemiluminescence (LucCL) assay on blood samples. Blood biochemistries were also measured simultaneously in hemodialysis patients 1 minute before and 5 minutes later in the presence or absence of intravenous injection of 300 mg ascorbic acid. Results: Ascorbic acid presented a strong antioxidant effect in DPPH chemical reaction. On the contrary, it exerted pro-oxidant effect when mixed with plasma or whole blood of healthy subjects and hemodialysis patients. The pro-oxidant effect of ascorbic acid detected by LucCL was attenuated by various iron chelators and superoxide dismutase. In hemodialysis patients, the changes of LucCL intensity were significantly higher in the ascorbic acid-treated group than those in the control group (1261.0 ± 401.9 v 77.4 ± 62.5 relative light unit [RLU]; P <0.05). Adjuvant ascorbic acid therapy resulted in significantly higher LucCL intensity in hemodialysis patients with ferritin ≥600 ng/mL (1,348.2 pmol/L) than those with ferritin less than 600 ng/mL (2,296.0 ± 763.8 v 414.3 ± 88.0 RLU; P <0.05). The changes of LucCL intensity were positively correlated with serum ferritin level (R2 = 0.8673; P <0.05). However, there was no significant correlation between the responses of LucCL intensity to ascorbic acid administration and transferrin saturation (R2 = 0.195; P = 0.0665). Conclusion: Persons with excess ascorbic acid supplement in the blood or plasma generate iron-chelator-suppressible chemiluminescents suggestive of free radical formation. Whether the findings occur in vivo or that the free radicals generated in vitro lead to toxicity in patients is not known from this study. These results suggest that either lower parenteral dose or lower infusion rate of ascorbic acid may be more appropriate for adjuvant therapy in iron-overloaded uremic patients.

Original languageEnglish
Pages (from-to)158-166
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume42
Issue number1 SUPPL. 2
DOIs
Publication statusPublished - Jul 1 2003
Externally publishedYes

Fingerprint

Ferritins
Ascorbic Acid
Renal Dialysis
Oxidative Stress
Luminescence
Serum
Free Radicals
Reactive Oxygen Species
Iron
Chelating Agents
In Vitro Techniques
Healthy Volunteers
Light
Iron Overload
Transferrin
Erythropoietin
Intravenous Injections
Biochemistry
Superoxide Dismutase
10,10'-dimethyl-9,9'-biacridinium

Keywords

  • Ascorbic acid
  • Ferritin
  • Hemodialysis (HD)
  • Oxidative stress

ASJC Scopus subject areas

  • Nephrology

Cite this

Effect of ascorbic acid administration in hemodialysis patients on in vitro oxidative stress parameters : Influence of serum ferritin levels. / Chen, Wei Teing; Lin, Yuh Feng; Yu, Fu Chiu; Kao, Woei Yau; Huang, Wen Hsin; Yan, Horng Chin.

In: American Journal of Kidney Diseases, Vol. 42, No. 1 SUPPL. 2, 01.07.2003, p. 158-166.

Research output: Contribution to journalArticle

Chen, Wei Teing ; Lin, Yuh Feng ; Yu, Fu Chiu ; Kao, Woei Yau ; Huang, Wen Hsin ; Yan, Horng Chin. / Effect of ascorbic acid administration in hemodialysis patients on in vitro oxidative stress parameters : Influence of serum ferritin levels. In: American Journal of Kidney Diseases. 2003 ; Vol. 42, No. 1 SUPPL. 2. pp. 158-166.
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abstract = "Background: Ascorbic acid supplementation has been recommended to circumvent resistance to erythropoietin, which sometimes occurs in iron-overloaded uremic patients. In considering the pro-oxidant effect of ascorbic acid, the authors hypothesize that adjuvant therapy with larger doses of ascorbic acid in hemodialysis patients with iron overload may raise the risk of increasing free radical generation. The oxidative stress of intravenous ascorbic acid supplementation in hemodialysis patients was evaluated in this study. Methods: Six healthy subjects and 29 hemodialysis patients were enrolled. Chemical scavenging activity of various compounds was measured by in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Free radical generation was determined in vitro by lucigenin-enhanced chemiluminescence (LucCL) assay on blood samples. Blood biochemistries were also measured simultaneously in hemodialysis patients 1 minute before and 5 minutes later in the presence or absence of intravenous injection of 300 mg ascorbic acid. Results: Ascorbic acid presented a strong antioxidant effect in DPPH chemical reaction. On the contrary, it exerted pro-oxidant effect when mixed with plasma or whole blood of healthy subjects and hemodialysis patients. The pro-oxidant effect of ascorbic acid detected by LucCL was attenuated by various iron chelators and superoxide dismutase. In hemodialysis patients, the changes of LucCL intensity were significantly higher in the ascorbic acid-treated group than those in the control group (1261.0 ± 401.9 v 77.4 ± 62.5 relative light unit [RLU]; P <0.05). Adjuvant ascorbic acid therapy resulted in significantly higher LucCL intensity in hemodialysis patients with ferritin ≥600 ng/mL (1,348.2 pmol/L) than those with ferritin less than 600 ng/mL (2,296.0 ± 763.8 v 414.3 ± 88.0 RLU; P <0.05). The changes of LucCL intensity were positively correlated with serum ferritin level (R2 = 0.8673; P <0.05). However, there was no significant correlation between the responses of LucCL intensity to ascorbic acid administration and transferrin saturation (R2 = 0.195; P = 0.0665). Conclusion: Persons with excess ascorbic acid supplement in the blood or plasma generate iron-chelator-suppressible chemiluminescents suggestive of free radical formation. Whether the findings occur in vivo or that the free radicals generated in vitro lead to toxicity in patients is not known from this study. These results suggest that either lower parenteral dose or lower infusion rate of ascorbic acid may be more appropriate for adjuvant therapy in iron-overloaded uremic patients.",
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T1 - Effect of ascorbic acid administration in hemodialysis patients on in vitro oxidative stress parameters

T2 - Influence of serum ferritin levels

AU - Chen, Wei Teing

AU - Lin, Yuh Feng

AU - Yu, Fu Chiu

AU - Kao, Woei Yau

AU - Huang, Wen Hsin

AU - Yan, Horng Chin

PY - 2003/7/1

Y1 - 2003/7/1

N2 - Background: Ascorbic acid supplementation has been recommended to circumvent resistance to erythropoietin, which sometimes occurs in iron-overloaded uremic patients. In considering the pro-oxidant effect of ascorbic acid, the authors hypothesize that adjuvant therapy with larger doses of ascorbic acid in hemodialysis patients with iron overload may raise the risk of increasing free radical generation. The oxidative stress of intravenous ascorbic acid supplementation in hemodialysis patients was evaluated in this study. Methods: Six healthy subjects and 29 hemodialysis patients were enrolled. Chemical scavenging activity of various compounds was measured by in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Free radical generation was determined in vitro by lucigenin-enhanced chemiluminescence (LucCL) assay on blood samples. Blood biochemistries were also measured simultaneously in hemodialysis patients 1 minute before and 5 minutes later in the presence or absence of intravenous injection of 300 mg ascorbic acid. Results: Ascorbic acid presented a strong antioxidant effect in DPPH chemical reaction. On the contrary, it exerted pro-oxidant effect when mixed with plasma or whole blood of healthy subjects and hemodialysis patients. The pro-oxidant effect of ascorbic acid detected by LucCL was attenuated by various iron chelators and superoxide dismutase. In hemodialysis patients, the changes of LucCL intensity were significantly higher in the ascorbic acid-treated group than those in the control group (1261.0 ± 401.9 v 77.4 ± 62.5 relative light unit [RLU]; P <0.05). Adjuvant ascorbic acid therapy resulted in significantly higher LucCL intensity in hemodialysis patients with ferritin ≥600 ng/mL (1,348.2 pmol/L) than those with ferritin less than 600 ng/mL (2,296.0 ± 763.8 v 414.3 ± 88.0 RLU; P <0.05). The changes of LucCL intensity were positively correlated with serum ferritin level (R2 = 0.8673; P <0.05). However, there was no significant correlation between the responses of LucCL intensity to ascorbic acid administration and transferrin saturation (R2 = 0.195; P = 0.0665). Conclusion: Persons with excess ascorbic acid supplement in the blood or plasma generate iron-chelator-suppressible chemiluminescents suggestive of free radical formation. Whether the findings occur in vivo or that the free radicals generated in vitro lead to toxicity in patients is not known from this study. These results suggest that either lower parenteral dose or lower infusion rate of ascorbic acid may be more appropriate for adjuvant therapy in iron-overloaded uremic patients.

AB - Background: Ascorbic acid supplementation has been recommended to circumvent resistance to erythropoietin, which sometimes occurs in iron-overloaded uremic patients. In considering the pro-oxidant effect of ascorbic acid, the authors hypothesize that adjuvant therapy with larger doses of ascorbic acid in hemodialysis patients with iron overload may raise the risk of increasing free radical generation. The oxidative stress of intravenous ascorbic acid supplementation in hemodialysis patients was evaluated in this study. Methods: Six healthy subjects and 29 hemodialysis patients were enrolled. Chemical scavenging activity of various compounds was measured by in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Free radical generation was determined in vitro by lucigenin-enhanced chemiluminescence (LucCL) assay on blood samples. Blood biochemistries were also measured simultaneously in hemodialysis patients 1 minute before and 5 minutes later in the presence or absence of intravenous injection of 300 mg ascorbic acid. Results: Ascorbic acid presented a strong antioxidant effect in DPPH chemical reaction. On the contrary, it exerted pro-oxidant effect when mixed with plasma or whole blood of healthy subjects and hemodialysis patients. The pro-oxidant effect of ascorbic acid detected by LucCL was attenuated by various iron chelators and superoxide dismutase. In hemodialysis patients, the changes of LucCL intensity were significantly higher in the ascorbic acid-treated group than those in the control group (1261.0 ± 401.9 v 77.4 ± 62.5 relative light unit [RLU]; P <0.05). Adjuvant ascorbic acid therapy resulted in significantly higher LucCL intensity in hemodialysis patients with ferritin ≥600 ng/mL (1,348.2 pmol/L) than those with ferritin less than 600 ng/mL (2,296.0 ± 763.8 v 414.3 ± 88.0 RLU; P <0.05). The changes of LucCL intensity were positively correlated with serum ferritin level (R2 = 0.8673; P <0.05). However, there was no significant correlation between the responses of LucCL intensity to ascorbic acid administration and transferrin saturation (R2 = 0.195; P = 0.0665). Conclusion: Persons with excess ascorbic acid supplement in the blood or plasma generate iron-chelator-suppressible chemiluminescents suggestive of free radical formation. Whether the findings occur in vivo or that the free radicals generated in vitro lead to toxicity in patients is not known from this study. These results suggest that either lower parenteral dose or lower infusion rate of ascorbic acid may be more appropriate for adjuvant therapy in iron-overloaded uremic patients.

KW - Ascorbic acid

KW - Ferritin

KW - Hemodialysis (HD)

KW - Oxidative stress

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