Preventive prospective of triclosan and triclosan-liposomal nanoparticles against experimental infection with a cystogenic ME49 strain of Toxoplasma gondii

El-Zawawy, Lobna A; El-Said, Doaa; Mossallam, Shereen F.; Ramadan, Heba S.; Younis, Salwa S

doi:10.1016/j.actatropica.2014.09.020

Cited by 25 publications

(10 citation statements)

References 58 publications

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“…In view of the urgent need for new medicines for toxoplasmosis treatment, the search for compounds with different mechanisms of action against T. gondii has been a target for many researchers (El-Zawawy et al ., 2015 a , 2015 b ; Montazeri et al ., 2017; Murata et al ., 2017). Drugs currently used for other purposes could be tested – alone or in combination – as alternative anti- T. gondii treatments (Shiojiri et al ., 2019; Zhang et al ., 2019).…”

Section: Introductionmentioning

confidence: 99%

Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain

et al. 2019

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This study evaluated the effects of rosuvastatin in vivo on toxoplasmosis chronic infection. Thirty-five Swiss mice were orally infected (ME-49 strain). After 50 days, the mice were separated into five groups: GI – non-infected, GII – infected, GIII – infected and treated with pyrimethamine and sulfadiazine (12.5 + 50 mg kg−1 body weight day−1), GIV and GV – infected and treated with rosuvastatin 10 and 40 mg kg−1 body weight day−1, respectively. After 21 days, we collected blood, liver, lungs, femoral biceps and brain were removed for Toxoplasma gondii DNA quantification by qPCR and histopathological analysis. GIV and GV did not present premature death or clinical changes, and the hepatic enzyme levels were lower compared to GI. Toxoplasma gondii DNA was detected mainly in brain and muscle, but the parasite load was significantly lower in GV compared to GII brains (P < 0.05). Histopathological changes were observed in brains, with T. gondii cysts as well as an inflammatory condition, including necrosis areas in GII and GIII. These data confirm active infection with tissue injury. This inflammatory condition was attenuated in the groups treated with rosuvastatin, especially R40 (GV). Our findings demonstrated the in vivo action of rosuvastatin in reducing cerebral parasitic load and indicate that this drug may interfere in chronic toxoplasmosis.

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Section: Introductionmentioning

confidence: 99%

Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain

et al. 2019

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“…However, parasite survival studies are either lacking or disappointing; triclosan did not extend mouse survival during a lethal challenge. This hydrophobic drug may hold greater promise if it can be more effectively delivered to the target enzyme (which resides in the parasite's quadruple-membraned organelle, the apicoplast): proofof-concept approaches investigated triclosan conjugated to octaarginine or encased in liposomal nanoparticles, the latter conferring greater reductions of parasite counts in peritoneal fluid than triclosan alone (45,46).…”

Section: Antimicrobial Agentsmentioning

confidence: 99%

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

Neville

Zach

Wang

et al. 2015

Antimicrob Agents Chemother

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e Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts.

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“…Accordingly, TS is proved as an effective, promising, and safe preventive drug against acute and chronic murine toxoplasmosis. Liposomal formulation of TS enhanced its efficacy and allowed its use at a lower dose (Surolia and Surolia, 2001; El-Zawawy et al, 2015a,b). Among apicoplast pathways, DNA replication is an important potential chemotherapeutic target.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review of In vitro and In vivo Activities of Anti-Toxoplasma Drugs and Compounds (2006–2016)

et al. 2017

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The currently available anti-Toxoplasma agents have serious limitations. This systematic review was performed to evaluate drugs and new compounds used for the treatment of toxoplasmosis. Data was systematically collected from published papers on the efficacy of drugs/compounds used against Toxoplasma gondii (T. gondii) globally during 2006–2016. The searched databases were PubMed, Google Scholar, Science Direct, ISI Web of Science, EBSCO, and Scopus. One hundred and eighteen papers were eligible for inclusion in this systematic review, which were both in vitro and in vivo studies. Within this review, 80 clinically available drugs and a large number of new compounds with more than 39 mechanisms of action were evaluated. Interestingly, many of the drugs/compounds evaluated against T. gondii act on the apicoplast. Therefore, the apicoplast represents as a potential drug target for new chemotherapy. Based on the current findings, 49 drugs/compounds demonstrated in vitro half-maximal inhibitory concentration (IC50) values of below 1 μM, but most of them were not evaluated further for in vivo effectiveness. However, the derivatives of the ciprofloxacin, endochin-like quinolones and 1-[4-(4-nitrophenoxy) phenyl] propane-1-one (NPPP) were significantly active against T. gondii tachyzoites both in vitro and in vivo. Thus, these compounds are promising candidates for future studies. Also, compound 32 (T. gondii calcium-dependent protein kinase 1 inhibitor), endochin-like quinolones, miltefosine, rolipram abolish, and guanabenz can be repurposed into an effective anti-parasitic with a unique ability to reduce brain tissue cysts (88.7, 88, 78, 74, and 69%, respectively). Additionally, no promising drugs are available for congenital toxoplasmosis. In conclusion, as current chemotherapy against toxoplasmosis is still not satisfactory, development of well-tolerated and safe specific immunoprophylaxis in relaxing the need of dependence on chemotherapeutics is a highly valuable goal for global disease control. However, with the increasing number of high-risk individuals, and absence of a proper vaccine, continued efforts are necessary for the development of novel treatment options against T. gondii. Some of the novel compounds reviewed here may represent good starting points for the discovery of effective new drugs. In further, bioinformatic and in silico studies are needed in order to identify new potential toxoplasmicidal drugs.

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Preventive prospective of triclosan and triclosan-liposomal nanoparticles against experimental infection with a cystogenic ME49 strain of Toxoplasma gondii

Cited by 25 publications

References 58 publications

Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain

Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

A Systematic Review of In vitro and In vivo Activities of Anti-Toxoplasma Drugs and Compounds (2006–2016)

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