| Title | Antioxidant Regulation of Oxidative Stress in Normal and Thalassemic Erythrocytes |
|---|---|
| Year | 1996 |
| Author | I.B. Afanas’ev; J.A. Osato; I. Afanas’ev; L.G. Korkina |
| Publisher | Conference on Oxidative Stress and Redox Regulation: Cellular Signaling, AIDS, Cancer and other Diseases |
Antioxidant Regulation of Oxidative Stress in Normal and Thalassemic Erythrocytes
Igor Afanas‘ev*, James Akira Osato, Ilya Afanas‘ev**, Ludmila Korkina***
*Vitamin Research Institute, ** Osato Research Foundation
***Russian Institute of Pediatric Hematology
It is known that the prooxidants quinones, phenylhydrazine, hydroperoxides, tansition metal ions, etc., stimulate oxygen radical production by erythrocytes. The release of active oxygen species is enhanced in erythrocytes under oxidative stress from patients with hematological disorders such as thalassemia. In this work we have studied the action of two types of free radical inhibitors, Bio-Normalizer (BN, a natural antioxidant prepared by the fermentation of Carica papaya) and 1-allyl-2-methyl-3-hydroxyl-4-pyridinone (AMHP, an oral chelator) on superoxide release by normal and thalassemic erythrocytes as well as hemoglobin oxidation and glutathione depletion in these cells. Oxidative stress in erythrocytes was induced by the addition of primaquine (PQ), menadione (vitamin K3, MD), its water-soluble derivative 1,4-naphthoquinone-2-methyl-3-sulfonate (HQMS), anticancer anthracycline antibiotic doxorubicin (Dox), and benzoquinone (BQ). We found that all prooxidants simulated superoxide release by erythrocytes (measured via cytochrome c reduction), the conversion of HbO2 into metHb, and the depletion of GSH. The effects of prooxidants on thalassemic erythrocytes were, as a rule, by 3-5 times greater than those on normal ones. Our results suggest that the prooxidanat attack on HbO2 led to the formation of superoxide ion which was converted into highly reactive hydroxyl radicals and was also able to oxidize GSH. Both the antioxidant BN and the chelator AMPH inhibited damaging free radical-mediated effects of prooxidants on erythrocytes. It was found that AMPH strongly suppressed superoxide release by thalassemic erythrocytes but only slightly affected that by normal ones. This fact supports the suggestion that excess “free” iron can be one of major factors of free radical-mediated damage in thalassemic erythrocytes. Thus, depending on their structures, antioxidants can suppress damaging effects of free radicals on different stages of destructive processes that point out at the possibility of using different antioxidants, free radical scavengers, and chelators for the regulation of free radical overproduction in different pathologic states.
(presented at the conference on Oxidative Stress and Redox Regulation: Cellular
Signaling, AIDS, Cancer and Other Disease, Paris, France, 21-24 May 1996)
Antioxidant Regulation of Oxidative Stress in Normal and Thalassemic Erythrocytes
Igor Afanas’ev*, James Akira Osato, Ilya Afanas’ev**, Ludmila Korkina***
*Vitamin Research Institute, ** Osato Research Foundation
***Rusian Institute of Pediatric Hematology
Erythrocytes are known to produce oxygen radicals when induced in vitro by prooxidants like quinones, phenylhydrazine, hydroperoxides and transition metal ions. Red blood cells also release active oxygen species during in vivo oxidative stress exemplified by hematological disorders such as thalassemia. In this experiment, the effect of two types of free radical inhibitors. Bio-Normalizer and 1-ally-2 methyl-3 -hydroxyl-4-pyridinone (AMHP, an oral chelator) on superoxide release by normal and thalassemic erythrocytes, as well as on hemoglobin oxidation were analyzed. Oxidative stress was induced by the addition of primaquine (PQ), menadione, 1,4-naphthoquinone-2-methyl-3-sulfonate (HQMS), doxorubicin and benzoquinone (BQ).
Bio-Normalizer and AMHP suppressed the damaging effect of Bio-Normalizer and AMHP inhibited superoxide release. With cytochrome c reduction test, it was found that both Bio-Normalizer and AMPH inhibited superoxide release. BN also decreased hemoglobin oxidation to methemoglobin. The findings imply the usefulness of Bio-Normalizer and AMHP in oxidative stress-related pathologies.
Antioxidant regulation of oxidative stress in normal and thalassemic erythrocytes
Afanas’ev I, Osato J, Afanas’ev, I and Korkina L
(presented at the conference on Oxidative Stress and Redox Regulation: Cellular
Signaling, AIDS, Cancer and Other Diseases, Paris, France, 21-24 May 1996)
Erythrocytes are known to produce oxygen radicals when induced in vitro by prooxidants like quinones, phenylhydrazine, hydroperoxides and transition metal ions. Red blood cells also release active oxygen species during in vivo oxidative stress exemplified by hematological disorders such as thalassemia. In this experiment, the effect of two types of free radical inhibitors, Bio-Normalizer and 1-allyl-2 methyl-3-hydroxy-4-pyridinone (AMHP, an oral chelator) on superoxide release by normal and thalassemic erythrocytes, as well as on hemoglobin oxidation were analyzed. Oxidative stress was induced by the addition of primaquine(PQ), menadione, 1,4-naphthoquinone-2-methyl-3-sulfonate (HQMS), doxorubicin and binzoquinone (BQ).
Bio-Normalizer and AMHP suppressed the damaging effect of the prooxidants used. With cytochrome c reduction test, it was found that both Bio-Normalizer and AMHP inhibited superoxide release. BN also decreased hemoglobin oxidation to methemoglobin. The findings imply the usefulness of Bio-Normalizer and AMHP in oxidative stress-related pathologies.