Encephalitozoon intestinalis: A new target for auranofin in a mice model

Abstract

Despite the fact that many approaches have been developed over years to find efficient and well-tolerated therapeutic regimens for microsporidiosis, the effectiveness of current drugs remains doubtful, and effective drugs against specific targets are still scarce. The present study is the first that was designed to evaluate the potency of auranofin, an anti-rheumatoid FDA approved drug, against intestinal Encephalitozoon intestinalis. Evaluation of the drug was achieved through counting of fecal and intestinal spores, studying the intestinal histopathological changes, measuring of intestinal hydrogen peroxide level, and post therapy follow-up of mice for 2 weeks for detection of relapse. Results showed that auranofin has promising anti-microsporidia potential. It showed a promising efficacy in mice experimentally infected with E. intestinalis. It has revealed an obvious reduction in fecal spore shedding and intestinal tissue spore load, amelioration of intestinal tissue pathological changes, and improvement of the local inflammatory infiltration without significant changes in hydrogen peroxide level. Interestingly, auranofin prevented the relapse of infection. Thus, considering the results of the present work, auranofin could be considered a therapeutic alternative for the gold standard drug ‘albendazole’ against the intestinal E. intestinalis infection especially in relapsing cases.

Gold(I) ion and the phosphine ligand are necessary for the anti- Toxoplasma gondii activity of auranofin

“…Auranofin, an FDA-approved drug for treating rheumatoid arthritis, has shown promising broad-spectrum antiparasitic activity ( 8 – 16 , 19 – 23 , 38 ) including anti- T. gondii activity, as we have previously demonstrated ( 18 , 25 ). Its chemical structure includes a gold(I) ion, a 2,3,4,6-tetra-O-acetyl-1-thio-β- D -glucopyranose ligand, and a triethylphosphine ligand ( Fig.…”

“…Recently, auranofin has emerged as a promising broad-spectrum antiparasitic agent, demonstrating activity against Plasmodium falciparum ( 8 ), Schistosoma mansoni ( 9 ), Leishmania spp . ( 10 , 11 ), Trypanosoma cruzi ( 12 ), Trichomonas vaginalis ( 13 – 15 ), Giardia lamblia ( 14 , 16 ), Entamoeba histolytica ( 17 ), T. gondii ( 18 ), free-living amoebas ( 19 – 21 ), Onchocerca ( 22 ), and Microsporidium ( 23 ) among other parasites of public health importance.…”

Repurposing auranofin for treatment of Experimental Cerebral Toxoplasmosis

“…It showed much accumulation in various tissues in addition to the ability to penetrate the blood brain barrier [15]. Side effects of the drug are usually self-limiting, including diarrhea, rash, and extremely rare thrombocytopenia [16]. Several studies proved also that it has a wide spectrum of biological properties including, anti-bacterial, anti-fungal, anti-viral and anti-parasitic effects [16,17].…”

“…Side effects of the drug are usually self-limiting, including diarrhea, rash, and extremely rare thrombocytopenia [16]. Several studies proved also that it has a wide spectrum of biological properties including, anti-bacterial, anti-fungal, anti-viral and anti-parasitic effects [16,17]. The anti-parasitic effect of auranofin has been demonstrated against Entamoeba histolytica, Naegleria fowleri, Giardia lamblia, Trypanosoma ssp, Leishmania spp and others [18][19][20][21][22].…”