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Antimalarial efficacy of methylene blue and menadione and their effect on glutathione metabolism of Plasmodium yoelii-infected albino mice

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Abstract

Plasmodium yoelii infection caused significant decline in the hepatic and splenic glutathione content and the activities of the key enzymes, that is, glutamate cysteine ligase (EC 6.3.2.2) and glutathione reductase (EC 1.8.1.7) of their murine host, that is, Swiss albino mice. Methylene blue as well as menadione were found to restore these constituents when given to P. yoelii-infected mice at the dose levels of 2.5 and 100 mg/kg, respectively, compared to mefloquine which does the same at 5.0 mg/kg dose. Methylene blue, like mefloquine also caused a rapid decline in percent parasitaemia, whereas menadione caused a delay in maturation of the infection, but could not cure the mice.

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Abbreviations

GSH:

Glutathione

GCL:

Glutamate cysteine ligase

GR:

Glutathione reductase

Mf:

Mefloquine

MB:

Methylene blue

Md:

Menadione

References

  1. Akerboom T, Bultmann T, Sies H (1988) Inhibition of taurocholate excretion during menadione metabolism in the perfused rat liver. Arch Biochem Biophys 263:10–18

  2. Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490

  3. DiMonte D, Ross D, Bellomo G, Eklöw L, Orrenuis S (1984) Alterations in intracellular thiol homeostasis during the metabolism of menadione by isolated rat hepatocytes. Arch Biochem Biophys 235:334–342

  4. Docampo R, Moreno SNJ (1984) Free radical metabolites in the mode of action of chemotherapeutic agents and phagocytic cells on Trypanosoma cruzi. Rev Infect Dis 6:223–228

  5. Eleff S, Kenneway NG, Buist NRM, Darley-Usmar VM, Capaldi RA, Bank WJ, Chance B (1984) 31 P-NMR study of improvement in oxidative phosphorylation by vitamin K3 and C in a patient with a defect in electron transport at complex III in skeletal muscles. Proc Natl Acad Sci 81:3529–3533

  6. Fairfield AS, Meshnick SR, Eaton JW (1983) Malarial parasites adopt host red cell superoxide dismutase. Science 221:764

  7. Famin O, Krugliak M, Ginsburg H (1999) Kinetics of inhibition of glutathione-mediated degradation of ferriprotoporphyrin IX by antimalarial drugs. Biochem Pharmacol 58:59 –68

  8. Färber PM, Arscott LD, Williams CH Jr, Becker K, Schirmer H (1998) Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett 422:311–314

  9. Gasser C (1959) Heinz body anemia and related phenomena. J Paediatr 54:673–690

  10. Ginsburg H, Atamna H (1994) The redox status of malaria-infected erythrocytes: an overview with an emphasis on unresolved problems. Parasite 1:5–13

  11. Goldstein BD (1974) Exacerbation of dapsone-induced Heinz body hemolytic anemia following treatment with methylene blue. Am J Med Sci 267:291–297

  12. Golenser J, Marva E, Chevion M (1991) The survival of Plasmodium under oxidant stress. Parasitol Today 7:142–146

  13. Harvey JW, Keitt AS (1983) Studies of the efficacy and potential hazards of methylene blue therapy in aniline-induced methaemoglobinaemia. Br J Haematol 54:29–41

  14. Hunt NH, Stocker R (1990) Oxidative stress and the redox status of malaria-infected erythrocytes. Blood Cells 16:499–530

  15. Jacob HS, Jandl JH (1966) Effects of sulfhydryl inhibition on red blood cells. III Glutathione in the regulation of hexose monophosphate pathway. J Biol Chem 241:4243–4250

  16. Kelner MJ, Alexander NM (1985) Methylene blue directly oxidizes glutathione without the intermediate formation of hydrogen peroxide. J Biol Chem 260:15168–15171

  17. Lopez-Shirley K, Zhang F, Gosser D, Scott M, Meshnick SR (1994) Antimalarial quinones: redox potential dependence of methemoglobin formation and hence release in erythrocytes. J Lab Clin Med 123:126–130

  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–276

  19. Meister A (1991) Glutathione deficiency produced by the inhibition of its synthesis, and its reversal: Applications in research and therapy. Pharmacol Therap 51:155–194

  20. Nickerson WJ, Falcone G, Strauss G (1963) Studies on the quinone-thioesters I. Mechanism of formation and properties of thiodione. Biochemistry 2:537–543

  21. Roth EF Jr, Raventos-Suarez C, Gilbert H, Stump D, Tanowitz H, Rowin KS, Nagel RL (1984) Oxidative stress and falciparum malaria: a critical review of the evidence. In: Eaton J, Brewer G (eds) Malaria and the red cell. Alan R. Liss, New York, p 35

  22. Schirmer RH, Schollhammer T, Eisenbrand G, Krauth-Siegel RL (1987) Oxidative stress as a defence mechanism against parasitic infections. Free Radic Res Commun 3:3–12

  23. Seelig GF, Meister A (1985) Glutathione biosynthesis: γ-glutamylcysteine synthetase from rat kidney. Methods Enzymol 113:379–392

  24. Vennerstrom JL, Makler MT, Angerhofer CK, Williams JA (1995) Antimalarial dyes revisited: Xanthenes, azines, oxazines and thiazines. Antimicrob Agents Chemother 39:2671–2677

  25. Wendel A (1981) In: Jakoby WB (ed) Enzymatic basis of detoxification. Academic Press, New York, pp 333–353

  26. White A, Handler P, Smith EL, Hill RL, Lehman IR (1978) Principles of biochemistry. 6th edn., pp. 112–114, 145–146

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Acknowledgements

Financial assistance in the form of Senior Research Fellowship to one of our authors (KA) from CSIR, New Delhi (India) and Volkswagen Stiftung, Hannover (Germany) in the form of ad hoc research grant to AKS for carrying out this research are gratefully acknowledged.

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Correspondence to Arvind K. Srivastava.

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Arora, K., Srivastava, A.K. Antimalarial efficacy of methylene blue and menadione and their effect on glutathione metabolism of Plasmodium yoelii-infected albino mice. Parasitol Res 97, 521–526 (2005). https://doi.org/10.1007/s00436-005-1478-4

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Keywords

  • Methylene Blue
  • Glutathione Reductase
  • Methylene Blue
  • GSSG
  • Mefloquine