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PLoS Neglected Tropical Diseases Jul 2023Although, approximately 30% of the world's population is estimated to be infected with Toxoplasma gondii (T. gondii) with serious manifestations in immunocompromised...
Zinc oxide nanoparticles produced by Zingiber officinale ameliorates acute toxoplasmosis-induced pathological and biochemical alterations and reduced parasite burden in mice model.
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.
Topics: Female; Mice; Animals; Zingiber officinale; Zinc Oxide; Parasites; Antioxidants; Toxoplasmosis; Nanoparticles; Toxoplasma; Disease Models, Animal
PubMed: 37410712
DOI: 10.1371/journal.pntd.0011447 -
Tropical Medicine & International... Jun 2024Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy...
BACKGROUND
Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii and is responsible for gestational and congenital infections worldwide. The current standard therapy is based on the administration of Spiramycin to prevent trans-placental transmission. Other therapies are being studied to reduce the rates of foetal transmission and symptomatic congenital infection.
OBJECTIVES
We report our long-standing experience in maternal toxoplasmosis infection treatment using a combination of Spiramycin-Cotrimoxazole, assessing its effectiveness in preventing vertical transmission compared to the expected incidence of congenital infection.
METHODS
We retrospectively collected cases of pregnant women referred to our centre for suspected toxoplasmosis infection according to Lebech criteria, treated with Spiramycin-Cotrimoxazole.
RESULTS
Of 1364 women referred to our centre, postnatal follow-up of primary toxoplasmosis was available in 562 cases (73.9%). The overall vertical transmission rate was 3.4% in women treated immediately with Spiramycin-Cotrimoxazole after the diagnosis of infection. In comparison, it was 7.7% in women undergoing the same therapy but late or with poor compliance. The foetal transmission rate was 71.4% in untreated cases. All the infected newborns of mother treated adequately with Spiramycin-Cotrimoxazole were asymptomatic afterbirth, while 6/21 infected infants of the inadequate Spiramycin-Cotrimoxazole therapy group had postnatal sequelae (28.5%). The incidence of transmission after appropriate Spiramycin-Cotrimoxazole therapy was significantly lower than the expected rate reported in literature.
CONCLUSIONS
A combination of Spiramycin and Cotrimoxazole is safe and effective in preventing foetal congenital toxoplasmosis and reducing sequelae in case of in-utero infection. The timing and adherence to the therapy are crucial to lowering the risk of congenital infection and neonatal morbidity.
PubMed: 38842439
DOI: 10.1111/tmi.14021 -
Chinese Journal of Natural Medicines Mar 2024Carrimycin (CA), sanctioned by China's National Medical Products Administration (NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to...
Carrimycin (CA), sanctioned by China's National Medical Products Administration (NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to exhibit multifaceted biological activities, encompassing anti-inflammatory, antiviral, and anti-tumor properties. Despite these applications, its efficacy in sepsis treatment remains unexplored. This study introduces a novel function of CA, demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in mice models. Our research employed in vitro assays, real-time quantitative polymerase chain reaction (RT-qPCR), and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines, namely tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6), in response to LPS stimulation. Additionally, Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B (NF-κB) activation in LPS-stimulated RAW264.7 cells. Complementing these findings, in vivo experiments demonstrated that CA effectively alleviates LPS- and CLP-triggered organ inflammation in C57BL/6 mice. Further insights were gained through 16S sequencing, highlighting CA's pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways, particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP. Notably, a comparative analysis revealed that CA's anti-inflammatory efficacy surpasses that of equivalent doses of aspirin (ASP) and TIENAM. Collectively, these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment. This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.
Topics: Mice; Animals; Lipopolysaccharides; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha; Interleukin-6; Punctures; Sepsis; Anti-Inflammatory Agents; Disease Models, Animal; Spiramycin
PubMed: 38553191
DOI: 10.1016/S1875-5364(24)60600-X -
Applied Biochemistry and Biotechnology Mar 2024Streptomyces, a prominent genus within the Actinomycetota phylum, is responsible for over 60% of clinically relevant antibiotics. Streptomyces strains inhabiting plant...
Streptomyces, a prominent genus within the Actinomycetota phylum, is responsible for over 60% of clinically relevant antibiotics. Streptomyces strains inhabiting plant roots possess the potential to synthesize bioactive natural products, conferring defense and resilience to plants against pathogenic microorganisms. However, this potential remains largely unexplored. This study aims to screen for bioactive metabolites produced by Streptomyces strains in the plant rhizosphere.Six Streptomyces isolates were cultivated using three modified media to induce the production of diverse metabolites, employing the One Strain Many Compounds (OSMAC) approach. The metabolites present in extracts from fermentation broths were examined through a non-targeted Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach coupled with Global Natural Products Social Molecular Networking (GNPS MN). The antimicrobial activity of the extracts was assessed using the disc diffusion method.The strains demonstrated a wide-ranging antimicrobial efficacy against all examined organisms. The GNPS molecular network analyses reveal that metabolite profiles in extracts can exhibit variations based on the medium and solvent system employed. Notably, the ethyl acetate and dichloromethane extracts from Streptomyces sp. CAH29, cultivated in Glucose-Yeast Extract Medium (GYM), exhibited inhibition diameters of up to 30 mm against both Staphylococcus aureus and Candida albicans. Within the metabolomes of these strains, the antibiotics spiramycin and actinomycin were detected. Additionally, lyngbatoxin, a tumor promoter, and potential new analogs were identified. Significantly, a considerable portion of the produced metabolites did not align with any known compounds, indicating the existence of unidentified metabolites generated by these strains. This suggests the possibility of introducing novel chemical entities.Our study illustrated that Streptomyces strains associated with plant roots could be considered a valuable source of bioactive secondary metabolites. Furthermore, the metabolomics approach utilized in this study serves as a rapid and valuable tool for the screening of microorganisms capable of producing bioactive metabolites.
PubMed: 38512549
DOI: 10.1007/s12010-024-04905-7 -
Journal of Parasitic Diseases :... Sep 2023is an opportunistic intracellular protozoon which may cause severe disease in the immunocompromised patients. Unfortunately, the majority of treatments on the market...
is an opportunistic intracellular protozoon which may cause severe disease in the immunocompromised patients. Unfortunately, the majority of treatments on the market work against tachyzoites in the acute infection but can't affect tissue cysts in the chronic phase. So, this study aimed to evaluate the effect of bee venom (BV) loaded metal organic frameworks (MOFs) nanoparticles (NPs) for the treatment of chronic murine toxoplasmosis. Ninety laboratory Swiss Albino mice were divided into 9 groups (10 mice each); GI (negative control), GII (infected control), GIII-GXI (infected with Me49 strain of and treated); GIII (MOFs-NPs), GIV and GV (BV alone and loaded on MOFs-NPs), GVI and GVII (spiramycin alone and loaded on MOFs-NPs), GVIII and GIX (ciprofloxacin alone and loaded on MOFs-NPs). Parasitological examination of brain cyst count, histopathological study of brain, retina, liver, and kidney tissue sections and immunohistochemical (IHC) evaluation of liver was performed. Counting of brain cysts showed high statistically significant difference between the infected treated groups and GII. GV showed the least count of brain cysts; mean ± SD (281 ± 29.5). Histopathological examination revealed a marked ameliorative effect of BV administration when used alone or loaded MOFs-NPs. It significantly reduced tissue inflammation, degeneration, and fibrosis. IHC examination of liver sections revealed high density CD8 infiltration in GII, low density CD8 infiltration in GIII, GVI, GVII, GVIII, and GIX while GIV and GV showed intermediate density CD8 infiltration. BV is a promising Apitherapy against chronic toxoplasmosis. This effect is markedly enhanced by MOFs-NPs.
PubMed: 37520202
DOI: 10.1007/s12639-023-01602-w -
Journal of Enzyme Inhibition and... Dec 2023Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke...
Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: , molecular docking, molecular dynamics, and SAR studies.
Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against the human topoisomerase II-DNA complex. Followed by the MD simulations for 200 ns and MM-GBSA calculations. On the other hand, the antitumor activities of the most promising candidates were investigated against three cancer cell lines using doxorubicin (DOX) as a reference drug. Notably, spiramycin () and clarithromycin () showed promising anticancer potentials on the MCF-7 cell line. Moreover, azithromycin () and exhibited good anticancer potentials against the HCT-116 cell line. Finally, the TOP-2 enzyme inhibition assay was carried out to confirm the proposed rationale. Briefly, potent TOP-2 inhibitory potentials were recorded for erythromycin () and roxithromycin (). Additionally, a SAR study opened eyes to promising anticancer pharmacophores encountered by these antibiotics.HighlightsMolecular docking studies of 139 antibiotics against the topoisomerase II-DNA complex., , , , and were the most promising and commercially available candidates.Molecular dynamics simulations for 200 ns for the most promising five complexes.MM-GBSA calculations for the frontier five complexes. and showed promising anticancer potentials on the MCF-7 cell line, besides, and exhibited good anticancer potentials against the HCT-116 cell line.Potent TOP-2 inhibitory potentials were recorded for and .
Topics: Humans; Topoisomerase II Inhibitors; Molecular Docking Simulation; Molecular Structure; Antineoplastic Agents; Intercalating Agents; Anti-Bacterial Agents; Structure-Activity Relationship; Molecular Dynamics Simulation; Cell Line, Tumor; DNA; DNA Topoisomerases, Type II; Drug Screening Assays, Antitumor
PubMed: 36701269
DOI: 10.1080/14756366.2023.2171029 -
Parasite Immunology Dec 2023This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female...
This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n = 72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25 mg/g/day) for 14 days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n = 75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP + FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35 days post-infection in batch (III). Treatments lasted for 14 days, and mice were sacrificed 60 days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP + FA was significantly (p < .0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.
Topics: Female; Mice; Animals; Toxoplasma; Spiramycin; Ferula; Brain; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral; Encephalitis
PubMed: 37807942
DOI: 10.1111/pim.13014 -
Folia Microbiologica Aug 2023Microbial natural products are among the main sources of compounds used in the medical biotechnology field for the purpose of drug development. However, as antibiotic...
Microbial natural products are among the main sources of compounds used in the medical biotechnology field for the purpose of drug development. However, as antibiotic resistance in pathogenic microorganisms is known to be increasing dramatically, there exists a need to develop new antibiotics. Actinomycetia have proven to be a good source of biologically active compounds, although the rediscovery of previously known compounds significantly slows down the introduction of new antibiotics. As a consequence, increasing attention is being paid to the isolation of actinomycete strains from previously unexplored sources, which can significantly increase the likelihood of discovering new biologically active compounds. This study investigated the diversity and bioactive potential of 372 actinomycete strains isolated from the rhizosphere soil of Juniperus excelsa M. Bieb. The examined actinomycete strains belonged to 11 genera, namely, Actinoplanes, Actinorectispora, Amycolatopsis, Kribbella, Micrococcus, Micromonospora, Nocardia, Promicromonospora, Rhodococcus, Saccharopolyspora and Streptomyces. The bioactive potential of each isolated actinomycete strain was determined on the basis of its ability to produce antimicrobial metabolites against Gram-positive and Gram-negative bacteria and yeast. Some 159 strains (42.74%) exhibited antimicrobial activity against at least one of the tested microbial strains. The dereplication analysis of the extract of the Streptomyces sp. Je 1-651 strain, which exhibited strong antimicrobial activity, led to the annotation of spiramycins and stambomycins. Moreover, the phylogenetic analysis based on the 16S rRNA gene sequence of the Je 1-651 strain revealed it to be close to the S. ambofaciens.
Topics: Anti-Bacterial Agents; Juniperus; Rhizosphere; Phylogeny; RNA, Ribosomal, 16S; Soil; Gram-Negative Bacteria; Gram-Positive Bacteria; Anti-Infective Agents; Actinobacteria; Actinomycetales; Streptomyces; Soil Microbiology
PubMed: 36947395
DOI: 10.1007/s12223-023-01047-x -
Animals : An Open Access Journal From... Sep 2023Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the...
Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania Region, Italy by analysing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescriptions were collected according to the drug administration (systemic or topical) and the rationale for the treatment chosen. In the period under investigation, 166,879 drugs were prescribed of which 129,116 (73.4%) were antimicrobial. A total of 83,965 (65%) antibiotics were prescribed to dogs, 40,477 (31.4%) to cats, and 4674 (3.6%) to other companion animals. In dogs, 90.5% of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely prescribed class was fluoroquinolones. The antimicrobials prescribed were mainly metronidazole-spiramycin (29.7%), amoxicillin-clavulanic (19.6%), enrofloxacin and cephalexin in dogs (16.5%) and enrofloxacin (22.6%) and amoxicillin-clavulanic acid (21.4%) in cats. Based on the results, the widespread use of broad-spectrum antimicrobials and the use of molecules for which limitations should be observed according to the EMA guidelines has emerged.
PubMed: 37760269
DOI: 10.3390/ani13182869 -
Journal of Parasitic Diseases :... Mar 2024Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell...
Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly ( < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.
PubMed: 38440758
DOI: 10.1007/s12639-023-01635-1