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

• Published in: Food and waterborne parasitology Vol. 26; p. e00144
• Main Authors: Fadil, Khadyga Hussein Abdel, Mahmoud, Eman Mohammed, El-Ahl, Saedia Abdel Hady Sayed, Abd-Elaal, Amany Ahmed, El-Shafaey, Amal Abdel-Aziz M., Badr, Mohammed Sharaf El Din Zaky, Elesawy, Yasmine Fathy, M. Mahfoz, Amal, Hamed, Alshaimaa Mohamed Raafat, Abdel-Shafi, Iman Raafat, Reda, Ahmed M., Elsayed, Mohamed Diefallah Abdelmoneim, Abdeltawab, Magda Said Ahmed
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2022; Elsevier
• Subjects: Angiogenesis; CD31; Inflammation; T. spiralis; VEGF; Verapamil; CD31; Angiogenesis; Verapamil; Inflammation; T. spiralis; VEGF
• ISSN: 2405-6766; 2405-6766
• DOI: 10.1016/j.fawpar.2022.e00144

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. [Display omitted] •Verapamil reduces larval count during the muscle phase of trichinellosis.•The anti-inflammatory effect of verapamil is more prominent in the muscle phase.•Verapamil and ivermectin reduce microvessel density in T. spiralis-infected muscles.•Ivermectin is more potent on reducing VEGF mRNA expression than verapamil.