Direct and indirect antiparasitic effects of chloroquine against the virulent RH strain of Toxoplasma gondii: An experimental study

Gamea, Ghada A.; Elmehy, Dalia A.; Salama, Amina M.; Soliman, Nema A.; Afifi, Omayma K.; Elkaliny, Heba H; Gheit, Rehab E. Abo El; El-Ebiary, Ahmad A.; Tahoon, Dina; Elkholy, Reem; Shoeib, Sarah; Eleryan, Mohamed A; Younis, Salwa S

doi:10.1016/j.actatropica.2022.106508

Cited by 6 publications

(6 citation statements)

References 65 publications

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“…According to colloid stability ranking stated by Vishwakarma et al, [52], MNPs with ZP -35.5 mV (higher than ± 30 mV) exhibited better long-term stability than nZVI (-20.9 mV) due to increased electro-static repulsion. Despite the obvious reduction in parasite burden, SPI showed minimal effect on surface of tachyzoites, supporting earlier observation by Gamea et al, [59] who reported minimal surface irregularities of the tachyzoites. This could be attributed to the mechanism of action of SPI, as it binds to the 50S ribosomal subunit, preventing peptide chains elongation, and thus, inhibition of protein synthesis [60].…”

Section: Discussionsupporting

confidence: 89%

“…Despite the obvious reduction in parasite burden, SPI showed minimal effect on surface of tachyzoites, supporting earlier observation by Gamea et al ., [ 59 ] who reported minimal surface irregularities of the tachyzoites. This could be attributed to the mechanism of action of SPI, as it binds to the 50S ribosomal subunit, preventing peptide chains elongation, and thus, inhibition of protein synthesis [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic and antioxidant potential of bionanofactory Ochrobactrum sp.-mediated magnetite and zerovalent iron nanoparticles against acute experimental toxoplasmosis

Hezema,

Eltarahony,

Abdel Salam

2023

PLoS Negl Trop Dis

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The control of toxoplasmosis, a rampant one health disease, has been focussed on conventional antitoxoplasmic agents with their adverse outcomes, including serious side effects, treatment failure and emergence of drug resistant strains. Nanobiotechnology may provide a strong impetus for versatile alternative therapies against toxoplasmosis. Bionanofactory Ochrobactrum sp. strain CNE2 was recruited for the biosynthesis of functionalized magnetite iron nanoparticles (MNPs) and nanozerovalent iron (nZVI) under aerobic and anaerobic conditions and their therapeutic efficacy was evaluated against acute toxoplasmosis in murine model. The formation of self-functionalized spherical nanoparticles varied in size, identity and surface properties were substantiated. Mice were orally administered 20 mg/kg of each formulation on the initial day of infection and continued for seven consecutive days post infection (PI). Parasitological, ultrastructural, immunological, and biochemical studies were performed for assessment of therapeutic activity of biogenic iron nanoparticles (INPs). Parasitologically, MNPs showed the highest antitoxoplasmic efficacy in terms of 96.82% and 91.87% reduction in mean tachyzoite count in peritoneal fluid and liver impression smears, respectively. Lesser percentage reductions were recorded in nZVI-treated infected subgroup (75.44% and 69.04%). In addition, scanning electron microscopy (SEM) examination revealed remarkable reduction in size and extensive damage to the surface of MNPs-treated tachyzoites. MNPs-treated infected mice revealed a statistically significant increase in the serum levels of both interferon gamma (IFN-γ) to 346.2 ± 4.6 pg/ml and reduced glutathione (GSH) to 8.83 ± 0.30 mg/dl that subsequently exerted malondialdehyde (MDA) quenching action. MNPs showed a superior promising antitoxoplasmic activity with respect to both spiramycin (SPI) and nZVI. To best of our knowledge, this is the first study of a bio-safe oral iron nanotherapeutic agent fabricated via an eco-friendly approach that offers promising potential against acute experimental toxoplasmosis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Therapeutic and antioxidant potential of bionanofactory Ochrobactrum sp.-mediated magnetite and zerovalent iron nanoparticles against acute experimental toxoplasmosis

Hezema,

Eltarahony,

Abdel Salam

2023

PLoS Negl Trop Dis

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“…On the same line, Spiramycin was given at a dose of 200 mg/kg/day-at the same time daily-after being dissolved in 100 μL of saline [12,31]. Treatments were given orally with an esophageal tube starting at the same day of infection [32][33][34] for 5 consecutive days [35][36][37]. After the end of treatments, mice were sacrificed on the 6 th day post infection for evaluation of the efficacy of the used drugs.…”

Section: Experimental Design and Animal Groupingmentioning

confidence: 99%

Zinc oxide nanoparticles produced by Zingiber officinale ameliorates acute toxoplasmosis-induced pathological and biochemical alterations and reduced parasite burden in mice model

et al. 2023

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Background Although, approximately 30% of the world’s population is estimated to be infected with Toxoplasma gondii (T. gondii) with serious manifestations in immunocompromised patients and pregnant females, the available treatment options for toxoplasmosis are limited with serious side effects. Therefore, it is of great importance to identify novel potent, well tolerated candidates for treatment of toxoplasmosis. The present study aimed to evaluate the effect of Zinc oxide nanoparticles (ZnO NPs) synthesized using Zingiber officinale against acute toxoplasmosis in experimentally infected mice. Methods The ethanolic extract of ginger was used to prepare ZnO NPs. The produced ZnO NPs were characterized in terms of structure and morphology using Fourier Transformed Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), UV- spectroscopy and scanning electron microscopy (SEM). The prepared formula was used in treatment of T. gondii RH virulent strain. Forty animals were divided into four groups, with ten mice per group. The first group was the uninfected, control group. The second group was infected but untreated. The third and the fourth groups received ZnO NPs and Spiramycin orally in a dose of 10 mg/kg and 200 mg/kg/day respectively. The effect of the used formulas on the animals survival rate, parasite burden, liver enzymes -including Alanine transaminase (ALT) and aspartate transaminase (AST)-, nitric oxide (NO) and Catalase antioxidant enzyme (CAT) activity was measured. Moreover, the effect of treatment on histopathological alterations associated with toxoplasmosis was examined. Results Mice treated with ZnO NPs showed the longest survival time with significant reduction in the parasite load in the livers and peritoneal fluids of the same group. Moreover, ZnO NPs treatment was associated with a significant reduction in the level of liver enzymes (ALT, AST) and NO and a significant increase in the antioxidant activity of CAT enzyme. SEM examination of tachyzoites from the peritoneal fluid showed marked distortion of T. gondii tachyzoites isolated from mice treated with ZnO NPs in comparison to untreated group. T. gondii induced histopathological alterations in the liver and brain were reversed by ZnO NPs treatment with restoration of normal tissue morphology. Conclusion The produced formula showed a good therapeutic potential in treatment of murine toxoplasmosis as demonstrated by prolonged survival rate, reduced parasite burden, improved T. gondii associated liver injury and histopathological alterations. Thus, we assume that the protective effect observed in the current research is attributed to the antioxidant capability of NPs. Based on the results obtained from the current work, we suggest greenly produced ZnO NPs as a chemotherapeutic agent with good therapeutic potential and high levels of safety in the treatment of toxoplasmosis.

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“…It was later fixed in glutaraldehyde. The samples were washed three times by flooding with large volumes of sterile distilled water, and then processed (Ramírez-Flores et al 2019;Gamea et al 2022) and examined using a JEOL JSM-IT200 scanning microscope in the Alexandria electron microscopy unit Alexandria Faculty of Science.…”

Section: %R =mentioning

confidence: 99%

The synergetic potential of Lactobacillus delbrueckii and Lactobacillus fermentum probiotics in alleviating the outcome of acute toxoplasmosis in mice

et al. 2023

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Toxoplasmosis is an immunologically complex disease, particularly in immunocompromised patients. Although there are several therapeutic regimens for such disease, the majority of them have many drawbacks. Therefore, it is of utmost importance to improve the current regimen in an effort to achieve a well-tolerated therapy while also enhancing the host immune response. Famous for their immunomodulatory effect, Lactobacillus delbrueckii and Lactobacillus fermentum probiotics were chosen to be evaluated in this study as an adjuvant therapy against the virulent RH Toxoplasma gondii (T. gondii) strain. Experimental mice were divided into control and treated groups. The control group was further subdivided into two groups: group I: 10 uninfected mice and group II: 20 infected untreated mice. The treated experimental group was subdivided into three groups (20 mice each); group III: sulfamethoxazole-trimethoprim (SMZ-TMP) treated, group IV: probiotics treated, and group V: SMZ-TMP combined with probiotics. The results obtained revealed that combined therapy increased survival rate and time up to 95% and 16 days, respectively, with an 82% reduction of tachyzoites and marked distortion, as detected by the scanning electron microscope (SEM). Additionally, combined therapy alleviated the severity and the extent of the inflammatory cells’ infiltration, thereby reducing hepatocyte degeneration. Intriguingly, serum IF-γ level showed a significant increase to 155.92 ± 10.12 ng/L with combined therapy, reflecting the immunological role of the combined therapy. The current results revealed that probiotics have a high adjuvant potential in alleviating the impact of toxoplasmosis. Using probiotics as a synergistic treatment to modulate conventional therapy in systemic toxoplasmosis may gain popularity due to their low cost and current availability.

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Direct and indirect antiparasitic effects of chloroquine against the virulent RH strain of Toxoplasma gondii: An experimental study

Cited by 6 publications

References 65 publications

Therapeutic and antioxidant potential of bionanofactory Ochrobactrum sp.-mediated magnetite and zerovalent iron nanoparticles against acute experimental toxoplasmosis

Therapeutic and antioxidant potential of bionanofactory Ochrobactrum sp.-mediated magnetite and zerovalent iron nanoparticles against acute experimental toxoplasmosis

Zinc oxide nanoparticles produced by Zingiber officinale ameliorates acute toxoplasmosis-induced pathological and biochemical alterations and reduced parasite burden in mice model

The synergetic potential of Lactobacillus delbrueckii and Lactobacillus fermentum probiotics in alleviating the outcome of acute toxoplasmosis in mice

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