Elevated glutathione accelerates oxidative damage to erythrocytes produced by aromatic disulfide.

It has been shown that certain dogs have erythrocytes characterized by an inherited high concentration of reduced glutathione (GSH), five to seven times the normal level (high-GSH RBCs). We examined whether increased GSH in dog erythrocytes leads to increased protection against oxidative damage induced by acetylphenylhydrazine (APH) and/or 4-aminophenyl disulfide (4-AD). When erythrocytes were incubated with 30 mmol/L APH, the Heinz body count was appreciably higher in normal RBCs than in high-GSH RBCs, while there was no difference in the increase of the methemoglobin (metHb) concentration in both RBCs. In contrast, both the Heinz body count and metHb production were much higher in high-GSH RBCs than in normal RBCs when erythrocytes were incubated with 4-AD. Furthermore, the generation of the superoxide in erythrocytes treated with 4-AD, which was measured by spin trapping combined with electron spin resonance (ESR), was obviously higher in high-GSH RBCs than in normal RBCs. These results clearly indicate that erythrocyte GSH is an important defense against oxidative damage induced by certain compounds such as APH, but that, in contrast, elevated GSH appears to accelerate oxidative damage to erythrocytes produced by aromatic disulfides, such as 4-AD, which generated a superoxide in erythrocytes via its redox reaction with GSH.

[1]  B. Britigan,et al.  Stimulated human neutrophils limit iron-catalyzed hydroxyl radical formation as detected by spin-trapping techniques. , 1986, The Journal of biological chemistry.

[2]  R. Munday.  Toxicity of aromatic disulphides. I. Generation of superoxide radical and hydrogen peroxide by aromatic disulphides in vitro , 1985, Journal of applied toxicology : JAT.

[3]  R. Munday.  Toxicity of aromatic disulphides. II. Intra‐erythrocytic hydrogen peroxide formation and oxidative damage by aromatic disulphides , 1985, Journal of applied toxicology : JAT.

[4]  J. Harvey,et al.  Experimental Onion-Induced Hemolytic Anemia in Dogs , 1985, Veterinary pathology.

[5]  M. Inaba,et al.  Increase of Na+ gradient-dependent L-glutamate and L-aspartate transport in high K+ dog erythrocytes associated with high activity of (Na+, K+)-ATPase. , 1984, The Journal of biological chemistry.

[6]  N. Taniguchi,et al.  Increase of Na-K-ATPase activity, glutamate, and aspartate uptake in dog erythrocytes associated with hereditary high accumulation of GSH, glutamate, glutamine, and aspartate , 1983 .

[7]  K. Kikugawa,et al.  Transformation of hemoglobin by various peroxides in vitro. , 1983, Chemical & pharmaceutical bulletin.

[8]  N. Taniguchi,et al.  Increase of Na-K-ATPase activity, glutamate, and aspartate uptake in dog erythrocytes associated with hereditary high accumulation of GSH, glutamate, glutamine, and aspartate. , 1983, Blood.

[9]  N. Taniguchi,et al.  Hereditary high concentration of glutathione in canine erythrocytes associated with high accumulation of glutamate, glutamine, and aspartate. , 1982, Blood.

[10]  J. Kaplan,et al.  Membrane-bound cytochrome b5 reductase (methemoglobin reductase) in human erythrocytes. Study in normal and methemoglobinemic subjects. , 1981, The Journal of clinical investigation.

[11]  C. Winterbourn,et al.  Protection by Ascorbate against Acetylphenylhydrazine‐Induced Heinz Body Formation in Glucose‐6‐Phosphate Dehydrogenase Deficient Erythrocytes , 1979, British journal of haematology.

[12]  R. Carrell,et al.  Mechanism of oxyhaemoglobin breakdown on reaction with acetylphenylhydrazine. , 1978, The Biochemical journal.

[13]  Y. Maede.  High concentration of blood glutathione in dogs with acute hemolytic anemia. , 1977, Nihon juigaku zasshi. The Japanese journal of veterinary science.

[14]  I. Fridovich,et al.  The oxidation of phenylhydrazine: superoxide and mechanism. , 1976, Biochemistry.

[15]  R. Carrell,et al.  Activated oxygen and haemolysis. , 1975, British journal of haematology.

[16]  Ernest Beutler,et al.  Red Cell Metabolism: A Manual of Biochemical Methods , 1975 .

[17]  A. Yoshida.  Hemolytic Anemia and G6PD Deficiency , 1973, Science.

[18]  B. Glader,et al.  Mechanism of methemoglobin formation by diphenylsulfones. Effect of 4-amino-4'-hydroxyaminodiphenylsulfone and other p-substituted derivatives. , 1972, Biochemical pharmacology.

[19]  E. Beutler.  Red cell metabolism , 1971 .

[20]  H. Shuval,et al.  A sensitive micromethod for the determination of methemoglobin in blood. , 1970, Clinica chimica acta; international journal of clinical chemistry.

[21]  K. V. van Kampen,et al.  Hemolytic anemia in sheep fed wild onion (Allium validum). , 1970, Journal of the American Veterinary Medical Association.

[22]  H. K. Prins,et al.  Congenital Nonspherocytic Hemolytic Anemia, Associated with Glutathione Deficiency of the Erythrocytes , 1966 .

[23]  P. Hochstein,et al.  GENERATION OF HYDROGEN PEROXIDE IN ERYTHROCYTES BY HEMOLYTIC AGENTS. , 1964, Biochemistry.

[24]  E. Beutler,et al.  Improved method for the determination of blood glutathione. , 1963, The Journal of laboratory and clinical medicine.

[25]  A. Leroux.  Membrane-bound Cytochrome b 5 Reductase ( Methemoglobin Reductase ) in Human Erythrocytes , 2022 .