Atorvastatin: In-Vivo Synergy with Metronidazole as Anti-Blastocystis Therapy

Abstract

Blastocystis is an enteric Straminopile in tropical, subtropical and developing countries. Metronidazole has been a chemotheraputic for blastocystosis. Failures in its regimens were reported and necessitate new studies searching for alternative therapeutic agents. Aim of current study is to investigate potential effects of Atorvastatin (AVA) compared to the conventional chemotherapeutic MTZ in experimentally Blastocystis-infected mice. Anti-Blastocystis efficacy of AVA was evaluated parasitologically, histopathologically and by transmission electron microscopy using MTZ (10 mg/kg) as a control. Therapeutic efficacy of AVA was apparently dose-dependent. Regimens of AVA (20 and 40 mg/kg) proved effective against Blastocystis infections with high reduction in Blastocystis shedding (93.4–97.9%) compared to MTZ (79.3%). The highest reductions (98.1% and 99.4%) were recorded in groups of combination treatments AVA 20–40 mg/kg and MTZ 10 mg/kg. Blastocystis was nearly eradicated by the 20th day post infection. Genotype analysis revealed that genotype I was most susceptible, genotype III was less. Histopathologic and ultrastructural studies revealed apoptotic changes in Blastocystis and significant improvement of intestinal histopathological changes more remarkable in combinational therapy groups. Thus, the present study offers AVA as a potential candidate for Blastocystis therapy combined with MTZ.

Therapeutic and Immuno-Modulatory Effect of Silver Nanoparticles-Loaded With Metronidazole on Experimental Blastocystosis

“…MTZ gave an acceptable effect with moderate Blastocystis cysts count reduction, moderate improvement of histopathological inflammatory changes and the immunological response. This was in accordance with the results of Basyoni et al (2018) 2014) reported complete failure of MTZ and reported that it should no longer be considered the recommended treatment for Blastocystis infection. Also, Batista et al (2017) found inadequate response to MTZ and their systematic review showed greatly variable responses to MTZ treatment ranging from 0% to 100.…”

Prenylquinones in Human Parasitic Protozoa: Biosynthesis, Physiological Functions, and Potential as Chemotherapeutic Targets

“…It was shown that the most widely used MVA pathway inhibitors for clinical applications, namely, mevastatin (also known as compactin or ML-236B) and mevinolin, affected trophozoite growth, an effect that could be reversed by the addition of mevalonate in the culture medium [106]. Even Blastocystis , Acanthamoeba and some apicomplexan parasites, including Toxoplasma , Cryptosporidium and Plasmodium , showed susceptibility to statins and apparent enzymatic capacity to metabolize MVA in protein extracts [76,77,84,107,108,109].…”

“…First of all, it was previously demonstrated that G. lamblia is sensitive to the statins mevastatin and mevinolin, two classical inhibitors of the MVA pathway and for consequence the isoprenic precursors synthesis [69,106]. In the case of Blastocystis , Acanthamoeba and some apicomplexan parasites, including Toxoplasma , Cryptosporidium and Plasmodium , it was demonstrated the susceptibility to several other statins and there is an evidence of enzymatic capacity to metabolize MVA in P. falciparum extracts [77,81,84,106,107,108]. Curiously, there is no evidence for pathways responsible for isoprenic chain biosynthesis in E. histolytica .…”

Blastocystis sp. puesta al día sobre su papel parasitario

“…debido a que este parásito afecta la integridad de la barrera epitelial del intestino, aumentando la permeabilidad por reorganización del epitelio de unión intestinal a través de la fosforilación de la cadena ligera de miosiona mediada por la Rho quinasa (ROCK); esto porque las estatinas protegen la integridad de la barrera epitelial por inhibición de ROCK, HMG-CoA reductasa y la cisteína proteasa. Específicamente de las estatinas como coadyuvante en el tratamiento de blastocistosis se han probado la atorvastatina y la lovastatina 39,49,50 .…”