Investigation of the effect of the calcium channel blocker, verapamil, on the parasite burden, inflammatory response and angiogenesis in experimental Trichinella spiralis infection in mice.

Autor:	Fadil KHA; Department of Medical Parasitology, Faculty of Medicine for Girls, Al- Azhar University, Cairo, Egypt., Mahmoud EM; Department of Medical Parasitology, Faculty of Medicine for Girls, Al- Azhar University, Cairo, Egypt., El-Ahl SAHS; Department of Medical Parasitology, Faculty of Medicine for Girls, Al- Azhar University, Cairo, Egypt., Abd-Elaal AA; Department of Medical Parasitology, Faculty of Medicine, Cairo University, Cairo, Egypt.; Postgraduate Department, Faculty of Medicine, Armed forces college of Medicine, Cairo, Egypt., El-Shafaey AAM; Department of Medical Parasitology, Faculty of Medicine for Girls, Al- Azhar University, Cairo, Egypt., Badr MSEDZ; Department of Molecular Biology, Medical Research Centre, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Elesawy YF; Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt., M Mahfoz A; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.; Egyptian Drug Authority, Giza, Egypt., Hamed AMR; Department of Medical Parasitology, Faculty of Medicine, Cairo University, Cairo, Egypt., Abdel-Shafi IR; Department of Medical Parasitology, Faculty of Medicine, Cairo University, Cairo, Egypt., Reda AM; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt., Elsayed MDA; Anatomy & Embryology Department, Faculty of Medicine, Cairo University, Cairo, Egypt., Abdeltawab MSA; Department of Medical Parasitology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Jazyk:	angličtina
Zdroj:	Food and waterborne parasitology [Food Waterborne Parasitol] 2022 Jan 22; Vol. 26, pp. e00144. Date of Electronic Publication: 2022 Jan 22 (Print Publication: 2022).
DOI:	10.1016/j.fawpar.2022.e00144
Abstrakt:	Trichinella spiralis larvae have very special characters that make them able to completely transform the function of the affected muscle cells towards a self-serving environment, offering them nourishment and protection via what is known as "nurse cells". This setting may be affected by drugs that are used for the treatment of co-morbidities and co-infections as calcium channel blockers, which are widely used in clinical practice. In the present study, the effects of verapamil, ivermectin (IVM), and their combined administration on the parasitic burden, immuno-pathology and angiogenesis were investigated during experimental trichinellosis. Estimation of intestinal adult parasitic stages and muscle larvae was done. VEGF gene expression and CD31 immunohistochemical local expression were measured to investigate angiogenesis, in addition to histopathological examination to explore the extent of inflammation. Although verapamil did not have an effect on the adult worm count during the intestinal phase, it induced an anti-inflammatory effect on intestinal pathology. During the muscle phase, it was very effective in reducing the larval count by 93.78%. IVM effectively reduced the worm count by 85.34%, and the muscle larval count by 97.84%, while combined verapamil and IVM administration resulted in a significant reduction in both adult parasites by 69.5% and larval stages by 99%. Both verapamil and IVM and their combination induced a potent decrease in local CD31 protein expression and VEGF gene expression. The important role of calcium and calcium channels during the pathology of trichinellosis, in addition to the pivotal role of calcium on biological processes such as immunity and angiogenesis, make calcium-channel blockers promising candidates for drug repurposing in the management of helminthic infection. Competing Interests: The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. (© 2022 The Authors.)
Databáze:	MEDLINE
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