Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hassan Z.R.; El-Sayed S.; Zekry K.M.; Ahmed S.G.; Abd-Elhamid A.H.; Salama D.E.A.; Taha A.K.; Mahmoud N.A.; Mohammed S.F.; Amin M.M.; Mohamed R.E.; Eraque A.M.S.; Mohamed S.A.; Abdelgalil R.M.; Atta S.A.; Fahmy N.T.; Badr M.S.

Journal: Parasitology Research

Publisher: Springer Science and Business Media Deutschland GmbH

Publication Date: 18 December 2023

Volume / Issue: Volume 123 / Issue 1

Article No.: 57

ISSN: 9320113

DOI: 10.1007/s00436-023-08077-x

Scopus: View on Scopus

PubMed: 38105357

Document Type: Article

Access: All Open Access; Green Open Access; Hybrid Gold Open Access

Authors and Affiliations

Hassan Z.R., Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; El-Sayed S., Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Zekry K.M., Department of Parasitology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Ahmed S.G., Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Abd-Elhamid A.H., Department of Histology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Salama D.E.A., Department of Pathology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt, Department of Pathology, School of Medicine, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo, 11829, Egypt; Taha A.K., Department of Pathology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Mahmoud N.A., Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Mohammed S.F., Department of Physiology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Amin M.M., Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Mohamed R.E., Department of Biochemistry, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Eraque A.M.S., Department of Biochemistry, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Mohamed S.A., Department of Biochemistry, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Abdelgalil R.M., Department of Anatomy and Embryology, Faculty of Medicine for Girls, Al-Azhar University, Yosief Abbas Street, Cairo, Kairo, Egypt; Atta S.A., Department of Immunology, Theodor Bilharz Research Institute, 36VF+MJ2, Warraq Al Arab, El Warraq, Giza Governorate, 3863130, Egypt; Fahmy N.T., Genomics, Egypt Center for Research and Regenerative Medicine (ECRRM), 3 Emtedad Ramses, Al Abbaseyah Al Gharbeyah, El Weili, Cairo Governorate, 4435102, Egypt; Badr M.S., Molecular Biology and Genetic-Bioinformatics Nano-Robot Diagnostics, Medical Research Centre, Faculty of Medicine, Ain Shams University, El-Khalyfa El-Mamoun Street Abbasya, Cairo, Egypt

Abstract

Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis. © 2023, The Author(s).

Keywords

Angiogenesis; Antioxidant; Atorvastatin; CD31; Ivermectin; Mesenchymal stem cells; Trichinellosis; Animals; Larva; Male; Mice; Trichinella spiralis; Vascular Endothelial Growth Factor A; glutathione; interleukin 17; lipid peroxidase; vasculotropin; vasculotropin A; adult; animal cell; animal experiment; animal model; animal tissue; Article; biochemical analysis; controlled study; gene expression; histopathology; immunofluorescence; immunohistochemistry; inflammation; mesenchymal stem cell; mouse; nonhuman; oxidative stress; Swiss Webster mouse; tissue injury; trichinosis; animal; parasitology

Citation Information

Scopus Citations: 4

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