Parasites, Hosts and Diseases

"glutathione"

Original Articles

Prostaglandin synthase activity of sigma- and mu-class glutathione transferases in a parasitic trematode, Clonorchis sinensis: Jiyoung Kim, Woon-Mok Sohn, Young-An Bae; Parasites Hosts Dis 2024;62(2):205-216.
Published online May 27, 2024; DOI: https://doi.org/10.3347/PHD.24004

Sigma-class glutathione transferase (GST) proteins with dual GST and prostaglandin synthase (PGS) activities play a crucial role in the establishment of Clonorchis sinensis infection. Herein, we analyzed the structural and enzymatic properties of sigma-class GST (CsGST-σ) proteins to obtain insight into their antioxidant and immunomodulatory functions in comparison with mu-class GST (CsGST-μ) proteins. CsGST-σ proteins conserved characteristic structures, which had been described in mammalian hematopoietic prostaglandin D₂ synthases. Recombinant forms of these CsGST-σ and CsGST-μ proteins expressed in Escherichia coli exhibited considerable degrees of GST and PGS activities with substantially different specific activities. All recombinant proteins displayed higher affinities toward prostaglandin H₂ (PGS substrate; average Km of 30.7 and 3.0 μm for prostaglandin D₂ [PGDS] and E₂ synthase [PGES], respectively) than those toward CDNB (GST substrate; average K_m of 1,205.1 μm). Furthermore, the catalytic efficiency (K_cat/K_m) of the PGDS/PGES activity was higher than that of GST activity (average K_cat/K_m of 3.1, 0.7, and 7.0×10^-3 s^-1μm^-1 for PGDS, PGES, and GST, respectively). Our data strongly suggest that the C. sinensis sigma- and mu-class GST proteins are deeply involved in regulating host immune responses by generating PGD₂ and PGE₂ in addition to their roles in general detoxification.

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Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice: Sayed Hassan Seif el-Din, Abdel-Nasser Abdel-Aal Sabra, Olfat Ali Hammam, Naglaa Mohamed El-Lakkany; Korean J Parasitol 2013;51(2):165-175.
Published online April 25, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.2.165

Abstract
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The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF.

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Brief Communications

Oxidative Stress in Vivax Malaria: Ramazan Bilgin, Mustafa S. Yalcin, Guzide Yucebilgic, Ismail S. Koltas, S?leyman Yazar; Korean J Parasitol 2012;50(4):375-377.
Published online November 26, 2012; DOI: https://doi.org/10.3347/kjp.2012.50.4.375

Abstract
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Malaria is still a leading cause of morbidity and mortality. The increase in lipid peroxidation reported in malaria infection and antioxidant status may be a useful marker of oxidative stress during malaria infection. The aim of this study was to investigate the role of antioxidant enzymes against toxic reactive oxygen species in patients infected with Plasmodium vivax and healthy controls. Malondialdehyde levels, superoxide dismutase, and glutathione peroxidase activities were determined in 91 P. vivax patients and compared with 52 controls. Malondialdehyde levels, superoxide dismutase, and glutathione peroxidase activities were 8.07±2.29 nM/ml, 2.69±0.33 U/ml, and 49.6±3.2 U/g Hb in the patient group and 2.72±0.50 nM/ml, 3.71±0.47 U/ml, and 62.3±4.3 U/g Hb in the control group, respectively. Malondialdehyde levels were found statistically significant in patients with vivax malaria higher than in healthy controls (P<0.001). On the other hand, superoxide dismutase and glutathione peroxidase activities were found to be significantly lower in vivax malaria patients than in controls (P<0.05). There was an increase in oxidative stress in vivax malaria. The results suggested that antioxidant defense mechanisms may play an important role in the pathogenesis of P. vivax.

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Glutathione Reductase and Thioredoxin Reductase: Novel Antioxidant Enzymes from Plasmodium berghei: Gaurav Kapoor, Harjeet Singh Banyal; Korean J Parasitol 2009;47(4):421-424.
Published online December 1, 2009; DOI: https://doi.org/10.3347/kjp.2009.47.4.421

Abstract
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Malaria parasites adapt to the oxidative stress during their erythrocytic stages with the help of vital thioredoxin redox system and glutathione redox system. Glutathione reductase and thioredoxin reductase are important enzymes of these redox systems that help parasites to maintain an adequate intracellular redox environment. In the present study, activities of glutathione reductase and thioredoxin reductase were investigated in normal and Plasmodium berghei-infected mice red blood cells and their fractions. Activities of glutathione reductase and thioredoxin reductase in P. berghei-infected host erythrocytes were found to be higher than those in normal host cells. These enzymes were mainly confined to the cytosolic part of cell-free P. berghei. Full characterization and understanding of these enzymes may promise advances in chemotherapy of malaria.

Citations

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Increased Blood Concentrations of Malondialdehyde in Plasmodium Infection: A Systematic Review and Meta-Analysis
Onchuma Mueangson, Aongart Mahittikorn, Nsoh Godwin Anabire, Wanida Mala, Manas Kotepui
Antioxidants.2023; 12(8): 1502. CrossRef
Genome-Wide CRISPR/Cas9 Screen Identifies New Genes Critical for Defense Against Oxidant Stress in Toxoplasma gondii
Yun Chen, Qi Liu, Jun-Xin Xue, Man-Yu Zhang, Xiao-Ling Geng, Quan Wang, Wei Jiang
Frontiers in Microbiology.2021;[Epub] CrossRef
Differential Effect of Antioxidants Glutathione and Vitamin C on the Hepatic Injuries Induced by Plasmodium berghei ANKA Infection
Nayara Kauffmann, Luana K. R. L. da Penha, Danielle V. Braga, Brenda J. A. Ataíde, Nivia S. F. Mendes, Laiane P. de Sousa, Givago S. da Souza, Adelaide C. F. Passos, Evander J. O. Batista, Anderson M. Herculano, Karen R. H. M. Oliveira, Praveen Bharti
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Lipid peroxidation and antioxidant enzymes activity in Plasmodium vivax malaria patients evolving with cholestatic jaundice
Camila Fabbri, Rita de Cássia Mascarenhas-Netto, Pritesh Lalwani, Gisely C Melo, Belisa ML Magalhães, Márcia AA Alexandre, Marcus VG Lacerda, Emerson S Lima
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Cysteine-3 and cysteine-4 are essential for the thioredoxin-like oxidoreductase and antioxidant activities of Plasmodium falciparum macrophage migration inhibitory factor
Athar Alam, Manish Goyal, Mohd. Shameel Iqbal, Samik Bindu, Sumanta Dey, Chinmay Pal, Pallab Maity, Nahren Manuel Mascarenhas, Nanda Ghoshal, Uday Bandyopadhyay
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Malondialdehyde, Glutathione, and Nitric Oxide Levels in Toxoplasma gondii Seropositive Patients: Ulku Karaman, Tuncay ?elik, Tugba Raika Kiran, Cemil Colak, Nilgun Ulfet Daldal; Korean J Parasitol 2008;46(4):293-295.
Published online December 20, 2008; DOI: https://doi.org/10.3347/kjp.2008.46.4.293

Abstract
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The aim of this study was to investigate the difference in the serum malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels between normal and T. gondii-infected patients. To this end, MDA, GSH, and NO levels in the sera of 37 seropositive patients and 40 participants in the control group were evaluated. In Toxoplasma ELISA, IgG results of the patient group were 1,013.0 ± 543.8 in optical density (mean ± SD). A statistically significant difference was found between patients and the control group in terms of MDA, GSH, and NO levels. A decrease in GSH activity was detected, while MDA and NO levels increased significantly. Consequently, it is suggested that the use of antioxidant vitamins in addition to a parasite treatment shall prove useful. The high infection vs control ratio of MDA and NO levels probably suggests the occurrence as a mechanism of tissue damage in cases of chronic toxoplasmosis. Moreover, it is recommended that the patient levels of MDA, GSH, and NO should be evaluated in toxoplasmosis.

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Original Article

Ultrastructural localization of 28 kDa glutathione S-transferase in adult Clonorchis sinensis: Sung-Jong Hong, Jae-Ran Yu, Shin-Yong Kang; Korean J Parasitol 2002;40(4):173-176.
Published online December 30, 2002; DOI: https://doi.org/10.3347/kjp.2002.40.4.173

Abstract
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Glutathione S-transferase (28GST) with molecular mass of 28 kDa is an anti-oxidant enzyme abundant in Clonorchis sinensis. In adult C. sinensis, 28GST was localized in tegumental syncytium, cytons, parenchyma, and sperm tails examined by immunoelectron microscopy. C. sinensis 28GST was earlier found to neutralize bio-reactive compounds and to be rich in eggs. Accordingly, it is suggested that 28GST plays important roles in phase II defense system and physiological roles in worm fecundity of C. sinensis.

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