The efficacy of resveratrol and nitazoxanide combination therapy in a murine model of chronic toxoplasmosis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hassan Z.R.; Zekry K.M.; El-Sayed S.; Ahmed S.G.; Taha A.K.; Mahmoud N.A.; Etewa M.A.M.; Mousa S.N.M.; Mohamed R.E.; Eraque A.M.S.; Mohamed S.A.; Amin Salman M.M.; Hamouda M.M.M.; Tolba A.M.A.; Nasr S.M.; Atta S.A.; Mohamed R.A.; Fahmy N.T.; Beshlawy H.A.; Badr M.S.

Journal: Journal of Parasitic Diseases

Publisher: Springer

Publication Date: 13 October 2025

Volume / Issue: Volume 49 / Issue 4

Pages: 1032–1044

ISSN: 9717196

DOI: 10.1007/s12639-025-01862-8

Scopus: View on Scopus

Document Type: Article

Authors and Affiliations

Hassan Z.R., Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt, Department of Parasitology, Faculty of Medicine, Benha National University (BNU) Qalyubia, Obour, Egypt; Zekry K.M., Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; El-Sayed S., Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Ahmed S.G., Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Taha A.K., Department of Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Mahmoud N.A., Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Etewa M.A.M., Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Mousa S.N.M., Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Mohamed R.E., Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Eraque A.M.S., Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Mohamed S.A., Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Amin Salman M.M., Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Hamouda M.M.M., Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Tolba A.M.A., Department of Anatomy and Embryology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; Nasr S.M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt, School of Biotechnology, Badr University in Cairo (BUC), Cairo, Badr City, Egypt; Atta S.A., Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt; Mohamed R.A., Department of Clinical and Chemical Pathology, Theodor Bilharz Research Institute, Giza, Egypt; Fahmy N.T., Department of Molecular Biology and Genomics, Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt; Beshlawy H.A., Department of Special Food and Nutrition, Food Technology Research Institute-Agricultural Research Center, Cairo, Egypt; Badr M.S., Department of Molecular Biology and Genetic-Bioinformatics Nano-Robot Diagnostics, Medical Research Centre, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Abstract

Toxoplasmosis is a global parasitic disease that can affect the central nervous system, causing severe complications. Introducing new agents that are safe during pregnancy and more effective for chronic toxoplasmosis is essential. This study investigated the effects of combined treatments with resveratrol, nitazoxanide, and spiramycin in chronic toxoplasmosis. Fifty-four Swiss albino mice were distributed into nine groups: Group 1, non-infected control; Group 2, infected non-treated control; Group 3, infected resveratrol-treated; Group 4, infected nitazoxanide-treated; Group 5, infected spiramycin-treated; Group 6, infected resveratrol and nitazoxanide-treated; Group 7, infected resveratrol and spiramycin-treated; Group 8, infected resveratrol, nitazoxanide, and spiramycin-treated; and Group 9, infected half-dose resveratrol, nitazoxanide, and spiramycin-treated. Effectiveness was evaluated by counting brain tissue cysts, histopathological examination of liver and brain tissues, immunohistochemical analysis of brain CD8+ T expression, biochemical measurement of serum IFN-γ and tissue MDA levels, and molecular assays for iNOS and BAX gene expression. The data demonstrated that adding resveratrol to spiramycin significantly reduced brain tissue cyst load, improved underlying tissue pathology, reduced brain CD8+ T expression, and lowered serum IFN-γ, tissue MDA, iNOS, and BAX gene levels in the liver, with elevated MDA, iNOS, and BAX gene levels in the brain. These results were enhanced by adding nitazoxanide to the resveratrol and spiramycin combination. It can be concoluded that co-administration of resveratrol and nitazoxanide can synergistically enhance the therapeutic effect of spiramycin in chronic toxoplasmosis. © Indian Society for Parasitology 2025.

Keywords

BAX; CD8<sup>+</sup> T; IFN-γ; iNOS; MDA; Nitazoxanide; Resveratrol; Spiramycin; Toxoplasmosis; inducible nitric oxide synthase; malonaldehyde; protein Bax; animal cell; animal experiment; animal model; animal tissue; Article; blood vessel; body weight; brain tissue; CD8+ T lymphocyte; central nervous system; controlled study; drug efficacy; enzyme linked immunosorbent assay; gene expression; histopathology; immunohistochemistry; liver tissue; male; mouse; murine model; nervous system; nonhuman; parasitosis; polymerase chain reaction; pregnancy; Western blotting

Citation Information

Scopus Citations: 1

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