Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities
Abstract
:1. Introduction
2. Characteristics of Toxoplasma gondii
2.1. Life Cycle
2.2. Routes of Toxoplasma Infection in Humans
2.3. Prophylaxis of Toxoplasma Infection in Humans
2.4. Toxoplasmosis Course in Humans
3. Oxidative Stress in Toxoplasma gondii Infection
3.1. Oxidant–Antioxidant Balance in Humans
3.2. Role of Oxidative Stress in Toxoplasma Infection
3.3. Antioxidant Defense of Toxoplasma gondii
3.4. Adaptative Response of Toxoplasma gondii to Oxidative Stress
3.5. Antioxidant Defense of the Host during Toxoplasma Infection
3.6. Oxidative Stress in the Early Stages of the Acute Phase of Toxoplasmosis
3.7. Oxidative Stress in the Later Stages of the Acute Phase of Toxoplasmosis
3.8. Oxidative Damage in the Host during Toxoplasma Infection
4. Oxidant–Antioxidant Effects in Toxoplasmosis Treatment
4.1. Inhibition of Antioxidant Defense of Toxoplasma gondii
4.2. Inorganic Nanoparticles
5. Plant-Derived Antioxidants in Toxoplasmosis Treatment
5.1. Tryptanthrin
5.2. Resveratrol and Selenium Compounds
5.3. Herb Extracts
5.4. Ursolic Acid Derivatives
6. Melatonin and Lipid-Soluble Vitamins in Toxoplasmosis Treatment
6.1. Melatonin Functions and Antioxidant Properties
6.2. Animal Model Studies on Melatonin in Toxoplasmosis
6.3. In Vitro Studies on Melatonin in Toxoplasmosis
6.4. Vitamin D Structure and Functions
6.5. Studies on Vitamin D in Toxoplasmosis
6.6. Vitamin E Functions and Antioxidant Properties
6.7. Studies on Vitamin E in Toxoplasmosis
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Models | Compound | IC50 /EC50 | Results/Oxidant–Antioxidant Effect | References |
---|---|---|---|---|
Human foreskin fibroblasts | tert-butyl hydroperoxide | IC50 = 100 ± 8 nM | • ↑ T. gondii parasites death • stable viability of the host cells • ↓ peroxiredoxin activity • changes in redox status of the parasites and destruction of their oxidant homeostasis | |
5-hydroxy-1,4-naphtoquinone (Juglon) | IC50 = 148 ± 6 nM | |||
Phenazine methyl sulfate | IC50 = 406 ± 134 nM | [57] | ||
Vero cell line from kidney of African green monkey | Extract of Azadirachta indica leaves | Toxoplasma elimination at concentrations higher than 2 mg/mL | • ↑ disorganization and elimination of intracellular tachyzoites • antioxidant effect on host cells | [114] |
Extract of Melia azedarach leaves | Toxoplasma elimination at concentrations higher than 0.5 mg/mL | • ↑ disorganization and elimination of intracellular tachyzoites • antioxidant effect on host cells | [113] | |
Human foreskin fibroblasts | 6-oximes of the tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) and its 8-bromoderivative | ID50 range (0.003 ÷ 1.3) µM | • anti-T. gondii activity • no host cell cytotoxicity • hepatoprotection of host cells • activation of the ERK-Nrf2 pathway • ↓ oxidative damage | [101,102,105] |
6-hydrazones of the tryptanthrin and its 8-bromoderivative | ID50 range (0.31 ÷ 12) µM | |||
6-hydroxy derivatives of the tryptanthrin and 8-bromotryptanthrin | ID50 range (0.002 ÷ 8.7) µM | |||
Vero cell line from kidney of African green monkey entry 4 | Extract of Psidium guajava (guava) | EC50 = 4.94 ± 0.039 µg/mL | • inhibition of T. gondii growth • no host toxicity • moderate antioxidant—inhibition of free radicals action in host cells | [110] |
Human foreskin fibroblasts | 1-thio-β-D-glucopyranosatotriethylphosphine gold-2,3,4,6-tetraacetate (Auranofin) | IC50 = 0.28 nM | • ↓ viability of T. gondii parasites • inhibition of thioredoxin reductase activity • ↓ resistance to oxidative damage | [55,93,94] |
LLC-MK2 host cells—kidney epithelial cells of rhesus monkey | [Fe(1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol)(SO4)]2 µ-oxo | IC50 = 3.6 µM nontoxic up to 200 µM | • inhibition of parasites growth at concentration for 2.5–25 µM • no effect on host cell viability • ↑ oxidative stress • ↓ metalloenzymes activity | [92] |
Human foreskin fibroblasts | Gold nanoparticles (AuNPs) | EC50 ≤ 7 µg/mL | • ↓ viability of the parasites • no host toxicity • alteration in redox status by ROS production and reduction in mitochondrial membrane potential | [97] |
Silver nanoparticles (AgNPs) | EC50 ≤ 1 µg/mL | |||
Platinum nanoparticles (PtNPs) | EC50 ≤ 100 µg/mL | |||
Vero cell line from kidney of African green monkey | Extract of Aloe vera | IC50 = 13.2 µg/mL | • anti-T. gondii activity in infected cells • ↓ MDA levels in host cells • potent antioxidant effect | [111] |
Extract of Eucalyptus globulus | IC50 = 24.7 µg/mL | |||
Human foreskin fibroblasts | Seed oil of the fruit of Cola gigantea | EC50 ≤ 15 µg/mL | • ↓ viability of T. gondii parasites • ↑ toxicity for parasites by ROS production • mild antioxidant potential in host cells | [112] |
GES-1 cells | Amide of 10-oxo derivative of ursolic acid and 1-H-tetrazol-5-amine | IC50 = 218.6 µM | • reduction of number of T. gondii invading of host cells • antioxidant effect on host cells | [115] |
Models | Compound | Dosage | Results/Oxidant–Antioxidant effect | References |
---|---|---|---|---|
Balb/c mice | Sulfamethoxazole/trimethoprim(S/T) supplemented with diphenyl diselenide or sodium selenite | S/T—0.5 mg/kg bid orally Na2O3Se—1 mg/kg intramuscularly | • ↓ viability of the parasites • ↓ TBARS and AOPP in liver samples • ↓ lipid peroxidation and protein oxidation in host organism | [109] |
S/T—0.5 mg/kg bid orally Ph2Se2—5 µmol/kg subcutaneously | ||||
Fourteen day old chicken embryos | 1-thio-β-D-glucopyranosatotriethylphosphine gold-2,3,4,6-tetraacetate (Auranofin) | 1 mg/kg a single dose | • protection from death in all acutely infected embryos • reduction of the parasite load in organs such as brain and liver • inhibition of thioredoxin reductase activity • ↓ resistance to oxidative damage | [55,93,94] |
Female mice | Diphenyl diselenide | 5 µmol/kg subcutaneously | • no reverse of the behavioral changes caused by the parasite • ↓ TBARS and ↑ GST in brain of the host • protective action as an antioxidant | [70] |
Female Balb/c mice | Extract of Aloe vera | 50/100 mg/kg/day orally | • ↑ survival rate of infected mice • ↓ MDA levels in host cells • potent antioxidant activity | [111] |
Extract of Eucalyptus globulus | 100/200 mg/kg/day orally | |||
Female Balb/c mice | Silver nanoparticles (AgNPs) green synthesized by Phoenix dactylifera (date palm) extract and Ziziphus spina-christi (Nabka) powder | 100 mg/kg/day orally | • ↑ survival rate of infected mice • ↓ lipid peroxidation, ↓ NO concentration in liver homogenate • ↑ GSH, SOD, CAT in liver homogenate | [83] |
Female KM mice | Amide of 10-oxo derivative of ursolic acid and 1-H-tetrazol-5-amine | 100 mg/kg/day oral gavage | • inhibition of tachyzoite growth in infected mice • restoration of the normal body weight of infected mice and reduction of hepatotoxicity • ↓ MDA levels and ↑ GSH • ↓ lipid peroxidation | [115] |
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Szewczyk-Golec, K.; Pawłowska, M.; Wesołowski, R.; Wróblewski, M.; Mila-Kierzenkowska, C. Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities. Int. J. Mol. Sci. 2021, 22, 5705. https://doi.org/10.3390/ijms22115705
Szewczyk-Golec K, Pawłowska M, Wesołowski R, Wróblewski M, Mila-Kierzenkowska C. Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities. International Journal of Molecular Sciences. 2021; 22(11):5705. https://doi.org/10.3390/ijms22115705
Chicago/Turabian StyleSzewczyk-Golec, Karolina, Marta Pawłowska, Roland Wesołowski, Marcin Wróblewski, and Celestyna Mila-Kierzenkowska. 2021. "Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities" International Journal of Molecular Sciences 22, no. 11: 5705. https://doi.org/10.3390/ijms22115705