Redox-Based Strategies against Infections by Eukaryotic Pathogens

Vallières, Cindy; Golinelli-Cohen, Marie-Pierre; Guittet, Olivier; Lepoivre, Michel; Huang, Meng‐Er; Vernis, Laurence

doi:10.3390/genes14040778

Cited by 7 publications

(3 citation statements)

References 83 publications

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“…This imbalance results from the excessive generation of reactive oxygen species (ROS) like the superoxide anion (O 2 ●− ), hydroxyl radicals (OH ● ), and hydrogen peroxide (H 2 O 2 ). O 2 ●− is the primary ROS produced from a variety of sources [ 4 ], while H 2 O 2 is not a radical but can generate OH ● via the Fenton reaction in the presence of Fe 2+ , which is one of the most harmful radicals in the human body [ 5 ]. Every cell possesses a mechanism that includes both non-enzymatic and enzymatic antioxidants that are able to neutralize excess ROS and protect against the harmful effects of oxidative stress [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Relationship between Antioxidant Enzymes, Oxidative Stress Markers, and Clinical Profile in Relapsing–Remitting Multiple Sclerosis

Bizoń,

Chojdak-Łukasiewicz,

Budrewicz

et al. 2023

Antioxidants

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We aimed to investigate the extent of alterations in the pro/antioxidant balance in the blood of patients with relapsing–remitting multiple sclerosis (RRMS) in relation to drug-modified therapy, gender, disability score, and disease duration. 161 patients (67 men and 94 women, aged 24–69 years, median 43.0) and 29 healthy individuals (9 men and 20 women, aged 25–68 years, median 41.0) were included in the study. We measured the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) as well as the concentration of interleukin-6 (IL-6), lipid peroxidation parameters (LPO), total oxidant status (TOS), and total antioxidant capacity (TAS). The activity of SOD did not show any significant differences between patients with RRMS and the control group in our study. In contrast, significant decreased GPx activity and increased CAT activity was observed in the blood of patients with RRMS compared to the control group. Additionally, the activity of CAT was influenced by gender and the use of disease-modifying therapies. Disease-modifying therapies also affected the concentration of TOS, TAS, and LPO. Our studies indicated that enhancing GPx activity may be more beneficial to providing potential therapeutic strategies aimed at modulating antioxidant defenses to mitigate oxidative stress in this disease.

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Section: Introductionmentioning

confidence: 99%

Exploring the Relationship between Antioxidant Enzymes, Oxidative Stress Markers, and Clinical Profile in Relapsing–Remitting Multiple Sclerosis

Bizoń,

Chojdak-Łukasiewicz,

Budrewicz

et al. 2023

Antioxidants

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“…In addition, several drugs currently used in chemotherapy for Chagas disease induce changes in the redox balance of these parasites [8]. Consequently, the systems involved in maintaining this balance, including Prxs, are important for ensuring survival and successful infection.…”

Section: Introductionmentioning

confidence: 99%

Overoxidation and Oligomerization of Trypanosoma cruzi Cytosolic and Mitochondrial Peroxiredoxins

Piñeyro,

Chiribao,

Arias

et al. 2023

Pathogens

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Peroxiredoxins (Prxs) have been shown to be important enzymes for trypanosomatids, counteracting oxidative stress and promoting cell infection and intracellular survival. In this work, we investigate the in vitro sensitivity to overoxidation and the overoxidation dynamics of Trypanosoma cruzi Prxs in parasites in culture and in the infection context. We showed that recombinant m-TXNPx, in contrast to what was observed for c-TXNPx, exists as low molecular mass forms in the overoxidized state. We observed that T. cruzi Prxs were overoxidized in epimastigotes treated with oxidants, and a significant proportion of the overoxidized forms were still present at least 24 h after treatment suggesting that these forms are not actively reversed. In in vitro infection experiments, we observed that Prxs are overoxidized in amastigotes residing in infected macrophages, demonstrating that inactivation of at least part of the Prxs by overoxidation occurs in a physiological context. We have shown that m-TXNPx has a redox-state-dependent chaperone activity. This function may be related to the increased thermotolerance observed in m-TXNPx-overexpressing parasites. This study suggests that despite the similarity between protozoan and mammalian Prxs, T. cruzi Prxs have different oligomerization dynamics and sensitivities to overoxidation, which may have implications for their function in the parasite life cycle and infection process.

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“…Therefore, disruption of the antioxidant systems of pathogens could serve as an effective strategy for the control of certain fungal pathogens including A. terreus . Enhancement of a pathogen’s oxidative stress using prooxidant compounds, administered alone or in combination with other antifungal drugs, has been proposed as a new therapeutic strategy [ 6 ].…”

mentioning

confidence: 99%