An ex vivo study of auranofin efficacy in the treatment of cryptosporidiosis

Document Type : Original Article

Authors

1 Department of Medical Parasitology, Faculty of Medicine, Tanta University, Tanta, Egypt

2 Department of Histology, Faculty of Medicine, Tanta University, Tanta, Egypt

Abstract

Background: Because Nitazoxanide (NTZ) shows limited efficacy in immunosuppressed individuals, a search for a safe and more effective alternative is urgently required. Auranofin (AUR) showed potent anti-inflammatory and anti-parasitic effects against numerous helminthic and protozoan parasites.
Objective: To evaluate the ex vivo effects of AUR on C. parvum in comparison with NTZ.
Material and Methods: Collected ileal explants were inoculated with excysted C. parvum oocysts in a dose of 104 oocysts/well. Six-well culture plates were used to grow 5 groups of ileal explants designated as two control groups (uninfected, and infected), and three treated groups (NTZ, AUR, and both drugs). The drugs were added six hours post-infection (PI). After 24 h of the drug treatment, explants from all groups were collected and processed for histopathological and ultrastructural assessments, and the culture supernatants were used for assessment of IFN-γ, IL-1β, IL-10, and thioredoxin reductase (TrxR) levels.
Results: Compared to infected control group, histopathological and ultrastructural examination revealed significant (P<0.001) restoration of the normal intestinal structure in the combined-treated group, followed by the AUR-treated group, while the NTZ group exhibited only partial improvement with persistent pathological changes in enterocytes, and marked ultrastructural abnormalities. Both NTZ and AUR showed significant (P<0.001) reduction in IFN-γ and IL-1β levels and a significant (P<0.001) increase in IL-10 levels. The addition of NTZ induced an insignificant elevation in TrxR levels in intestinal tissue compared to the infected control group. The lowest level of TrxR enzyme was recorded in the AUR group.
Conclusion: Our study concluded that AUR demonstrated superior anti-cryptosporidial, and anti-inflammatory efficacy compared to NTZ, likely due to its redox-modulating activity. The combination group showed the best results. Further in vivo studies, and human clinical trials are recommended.

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