The effect of some antimalarial drugs on Plasmodium berghei glutathione-S-transferase enzyme
Subject Areas : ParasitologyAlireza Sadeghi Tafreshi 1 , Sedigheh Sadeghi 2 , Maryam Hekmatipour 3 , Shaghayegh Shams 4 , Maryam Mohammadi 5 , Farideh Vahabi 6 , Mohammad Arjmand 7 , Zahra Zamani 8
1 - Ph.D. candidate, Department of Biochemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 - DMLT, Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
3 - M.Sc., Department of Biochemistry, Payame Noor University, East Tehran, Tehran, Iran.
4 - M.Sc., Department of Biochemistry, Payame Noor University, East Tehran, Tehran, Iran
5 - M.Sc., Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
6 - MD, Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.
7 - Associate Professor, Department of Biochemistry,
Pasteur Institute of Iran, Tehran, Iran.
8 - Associate Professor, Department of Biochemistry,
Pasteur Institute of Iran, Tehran, Iran.
Keywords: Plasmodium berghei, Eosin B, Combination drugs, Glutathione-S-transferase,
Abstract :
Glutathione-S-transferase (GST) are a group of enzymes found in all living organisms that contribute to detoxification of xenobiotic compounds via Phase II conjugation with glutathione and play an important role in drug resistance. The GST activity in chloroquine-resistant strains of rodent and human Plasmodium is meaningfully higher than sensitive strains. In the present study, the GST activity and level were measured in those mice infected with Plasmodium berghei during the treatment with antimalarial drugs. Mice infections were carried out by P. berghei and inhibition growth of the parasite was performed through three doses of eosin B and prevalent antimalarial drugs similarly artemisinin and sulfadoxine-pyrimethamine in 24 h based on Peter's test. Two hours after the last dose, the mice were bled, RBCs were isolated by cellulose column, and P. berghei was released after washing with saponin. The enzyme function was measured using glutathione and CDNB as substrate at 340 nm. In addition, the GST levels were assessed by Biotech kit. The GST specific activities and levels of P. berghei in infected mice treated with eosin B and sulfadoxine-pyrimethamine and their combination were decreased while such change was not seen in those ones treated with atemisinin and in combination with eosin B. Owing to the reduction property of the combination of eosin B on the GST which has a fundamental role in the resistance of the parasite to antimalarial drugs, it could be considered as a promising procedure for application in antimalarial combination drugs.
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2. Müller S. Role and regulation of glutathione metabolism in Plasmodium falciparum. Mol. 2015; 20(6):
10511-10534.
3. Lisewski AM. Plasmodium spp. membrane glutathione S-transferases: detoxification units and drug
targets. Microb Cell. 2014; 1(11): 387.
4. Fernandes RC, Hasan M, Gupta H, Geetha K, Rai PS, Hande MH, D’Souza SC, Adhikari P, Brand A,
Satyamoorthy K. Host genetic variations in glutathione-S-transferases, superoxide dismutases and
catalase genes influence susceptibility to malaria infection in an Indian population. Mol Genet
Genomics. 2015; 290(3): 1155-1168.
5. Sujitha V, Murugan K, Dinesh D, Pandiyan A, Aruliah R, Hwang JS, Kalimuthu K, Panneerselvam C,
Higuchi A, Kumar S, Alarfaj AA. Green-synthesized CdSnano-pesticides: toxicity on young instars of
malaria vectors and impact on enzymatic activities of the non-target mud crab Scylla serrata. Aquat
Toxicol. 2017; 188: 100-108.
6. Lumjuan N, McCarroll L, Prapanthadara LA, Hemingway J, Ranson H. Elevated activity of an Epsilon
class glutathione transferase confers DDT resistance in the dengue vector, Aedesaegypti. Insect
Biochem Mol. 2005; 35(8): 861-871.
7. Lu G, Nagbanshi M, Goldau N, Jorge MM, Meissner P, Jahn A, Mockenhaupt FP, Müller O. Efficacy
and safety of methylene blue in the treatment of malaria: a systematic review. BMC Med. 2018;
16(1): 59.
8. Bosson-Vanga H, Franetich JF, Soulard V, Sossau D, Tefit M, Kane B, Vaillant JC, Borrmann S, Müller
O, Dereuddre-Bosquet N, Grand R. Differential activity of methylene blue against erythrocytic and
hepatic stages of Plasmodium. Malaria J. 2018; 17(1): 143.
9. Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W, Elliott DA, Joiner
KA, Schirmer RH, Anderson KS. Eosin B as a novel antimalarial agent for drug-resistant Plasmodium
falciparum. Antimicrob Agents Chemother. 2006; 50(9): 3132-3141.
10. Zamani Z, Tafreshi AS, Nahrevanian H, Lame-Rad B, Pourfallah F, Eslamifar H, Sadeghi S, Vahabi F,
Iravani A, Arjmand M. Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model. Malaria
Res Treat. 2012; doi:10.1155/2012/381724.
11. Srivastava P, Puri SK, Kamboj KK, Pandey VC. Glutathione‐S‐transferase activity in malarial
parasites. Trop Med Int Health. 1999; 4(4): 251-254.
12. Kalita J, Shukla R, Shukla H, Gadhave K, Giri R, Tripathi T. Comprehensive analysis of the catalytic
and structural properties of a mu-class glutathione s-transferase from Fasciolagigantica. Sci Rep. 2017;
7(1): 17547.
13. Haschek WM, Rousseaux CG, Wallig MA, Bolon B, Ochoa R, editors. Haschek and Rousseaux's
handbook of toxicologic pathology. Academic Press; 2013; doi:10.1016/C2010-1-67850-9.
14. Li F, Wu H, Wang Q, Li X, Zhao J. Glutathione S-transferase (GST) gene expression profiles in two
marine bivalves exposed to BDE-47 and their potential molecular mechanisms. Chin J Oceanol Limn.
2015; 33(3): 705-713.
15. Sue M, Yajima S. Crystal structure of the delta-class glutathione transferase in Muscadomestica.
Biochem Bioph Res Co. 2018; 502(3): 345-350.
16. Akoachere M, Buchholz K, Fischer E, Burhenne J, Haefeli WE, Schirmer RH, Becker K. In vitro
assessment of methylene blue on chloroquine-sensitive and-resistant Plasmodium falciparum strains
reveals synergistic action with artemisinins. Antimicrob Agents Chemother. 2005; 49(11): 4592-4597.
17. Hiller N, Fritz‐Wolf K, Deponte M, Wende W, Zimmermann H, Becker K. Plasmodium falciparum
glutathione-S‐transferase- Structural and mechanistic studies on ligand binding and enzyme inhibition.
Protein Sci. 2006; 15(2): 281-289
_||_
docking. ComputBiol Chem. 2016; 64: 237-249.
2. Müller S. Role and regulation of glutathione metabolism in Plasmodium falciparum. Mol. 2015; 20(6):
10511-10534.
3. Lisewski AM. Plasmodium spp. membrane glutathione S-transferases: detoxification units and drug
targets. Microb Cell. 2014; 1(11): 387.
4. Fernandes RC, Hasan M, Gupta H, Geetha K, Rai PS, Hande MH, D’Souza SC, Adhikari P, Brand A,
Satyamoorthy K. Host genetic variations in glutathione-S-transferases, superoxide dismutases and
catalase genes influence susceptibility to malaria infection in an Indian population. Mol Genet
Genomics. 2015; 290(3): 1155-1168.
5. Sujitha V, Murugan K, Dinesh D, Pandiyan A, Aruliah R, Hwang JS, Kalimuthu K, Panneerselvam C,
Higuchi A, Kumar S, Alarfaj AA. Green-synthesized CdSnano-pesticides: toxicity on young instars of
malaria vectors and impact on enzymatic activities of the non-target mud crab Scylla serrata. Aquat
Toxicol. 2017; 188: 100-108.
6. Lumjuan N, McCarroll L, Prapanthadara LA, Hemingway J, Ranson H. Elevated activity of an Epsilon
class glutathione transferase confers DDT resistance in the dengue vector, Aedesaegypti. Insect
Biochem Mol. 2005; 35(8): 861-871.
7. Lu G, Nagbanshi M, Goldau N, Jorge MM, Meissner P, Jahn A, Mockenhaupt FP, Müller O. Efficacy
and safety of methylene blue in the treatment of malaria: a systematic review. BMC Med. 2018;
16(1): 59.
8. Bosson-Vanga H, Franetich JF, Soulard V, Sossau D, Tefit M, Kane B, Vaillant JC, Borrmann S, Müller
O, Dereuddre-Bosquet N, Grand R. Differential activity of methylene blue against erythrocytic and
hepatic stages of Plasmodium. Malaria J. 2018; 17(1): 143.
9. Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W, Elliott DA, Joiner
KA, Schirmer RH, Anderson KS. Eosin B as a novel antimalarial agent for drug-resistant Plasmodium
falciparum. Antimicrob Agents Chemother. 2006; 50(9): 3132-3141.
10. Zamani Z, Tafreshi AS, Nahrevanian H, Lame-Rad B, Pourfallah F, Eslamifar H, Sadeghi S, Vahabi F,
Iravani A, Arjmand M. Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model. Malaria
Res Treat. 2012; doi:10.1155/2012/381724.
11. Srivastava P, Puri SK, Kamboj KK, Pandey VC. Glutathione‐S‐transferase activity in malarial
parasites. Trop Med Int Health. 1999; 4(4): 251-254.
12. Kalita J, Shukla R, Shukla H, Gadhave K, Giri R, Tripathi T. Comprehensive analysis of the catalytic
and structural properties of a mu-class glutathione s-transferase from Fasciolagigantica. Sci Rep. 2017;
7(1): 17547.
13. Haschek WM, Rousseaux CG, Wallig MA, Bolon B, Ochoa R, editors. Haschek and Rousseaux's
handbook of toxicologic pathology. Academic Press; 2013; doi:10.1016/C2010-1-67850-9.
14. Li F, Wu H, Wang Q, Li X, Zhao J. Glutathione S-transferase (GST) gene expression profiles in two
marine bivalves exposed to BDE-47 and their potential molecular mechanisms. Chin J Oceanol Limn.
2015; 33(3): 705-713.
15. Sue M, Yajima S. Crystal structure of the delta-class glutathione transferase in Muscadomestica.
Biochem Bioph Res Co. 2018; 502(3): 345-350.
16. Akoachere M, Buchholz K, Fischer E, Burhenne J, Haefeli WE, Schirmer RH, Becker K. In vitro
assessment of methylene blue on chloroquine-sensitive and-resistant Plasmodium falciparum strains
reveals synergistic action with artemisinins. Antimicrob Agents Chemother. 2005; 49(11): 4592-4597.
17. Hiller N, Fritz‐Wolf K, Deponte M, Wende W, Zimmermann H, Becker K. Plasmodium falciparum
glutathione-S‐transferase- Structural and mechanistic studies on ligand binding and enzyme inhibition.
Protein Sci. 2006; 15(2): 281-289