Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally immunosuppressed mice

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Madbouly Taha N.; Salah A. Yousof H.-A.; El-Sayed S.H.; Younis A.I.; Ismail Negm M.S.

Journal: Experimental Parasitology

Publisher: Academic Press Inc.

Publication Date: October 2017

Volume / Issue: Volume 181

Pages: 57–69

ISSN: 144894

DOI: 10.1016/j.exppara.2017.07.010

Scopus: View on Scopus

PubMed: 28764965

Document Type: Article

Authors and Affiliations

Madbouly Taha N., Medical Parasitology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt; Salah A. Yousof H.-A., Medical Parasitology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt; El-Sayed S.H., Theodor Bilharz Research Institute, Imbaba, Giza, Egypt; Younis A.I., Medical Parasitology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt; Ismail Negm M.S., Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt

Abstract

The present study was conducted on 200 male mice for the detection of the effect of Atorvastatin on Cryptosporidium spp. infection versus the commercially used drug Nitazoxanide in experimentally immunosuppressed mice. Atorvastatin was used alone at low dose (20 mg/kg), high dose (40 mg/kg), and combined with Nitazoxanide (1000 mg/kg) with either the low dose or high dose for five consecutive days. Parasitological assessment of the drug effect was done using Modified Z-N staining of stool samples collected from mice. Results revealed a reduction of the number of oocysts shed with percentage of reduction on the 21st day post infection by 53.7%, 67.2%, 70.1% & 77.5%, respectively, compared to the infected untreated group. The Nitazoxanide treated group showed 52.7% reduction. In addition, examination of small and large intestinal contents after mice scarification revealed reduced numbers of oocysts by 56.2%-58.8%, 65.1%-65.3%, 70.6%-73.9% and 77.8%-79.9%, respectively, compared to 51.2%-54.1% in Nitazoxanide treated group. The histopathological examination of sections from duodenum, jejunum, ileum, colon, stomach and lungs also revealed a significant improvement of the histopathological changes in Atorvastatin treated groups and more remarkable improvement in the groups treated with combined drugs as compared to infected untreated group. Accordingly, the combination of Atorvastatin and Nitazoxanide showed a synergistic effect through reduction of the number of oocysts shed and improvement of the histopathological changes induced by Cryptosporidium spp. infection in the small intestine, colon, stomach and lungs of infected immunosuppressed mice in comparison to that induced by either Nitazoxanide or Atorvastatin alone. © 2017 Elsevier Inc.

Keywords

Atorvastatin; Cryptosporidium; Drug effects; Histopathological assessment; Immunosuppressed mice; Nitazoxanide; Animals; Antiparasitic Agents; Atorvastatin Calcium; Colon; Cryptosporidiosis; Drug Synergism; Duodenum; Feces; Gallbladder; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ileum; Immunosuppression; Jejunum; Lung; Male; Mice; Stomach; Tablets; Thiazoles; antiparasitic agent; hydroxymethylglutaryl coenzyme A reductase inhibitor; tablet; thiazole derivative; animal experiment; animal model; animal tissue; Article; controlled study; dose response; drug effect; drug megadose; drug potentiation; drug structure; experimental mouse; feces analysis; gastrointestinal infection; histopathology; immune deficiency; intestine infection; low drug dose; lung infection; mouse; nonhuman; oocyst; priority journal; animal; immunology; immunosuppressive treatment; parasitology; pathology

Citation Information

Scopus Citations: 41

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