The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods

Background: Methenamine is a worldwide antibacterial agent for urinary system infections in human and animals. The effect of methenamine consumption during early phase of pregnancy is not fully clarified in previous studies. Vascular development is the essential part of the early embryonic growth.
Objective: In this study, we used chicken chorioallantoic membrane to evaluate the effects of methenamine administration on angiogenesis process as a model.
Materials and Methods: In this experimental study, 20 Ross 308 eggs (mean weight 55 ± 4) were incubated. The eggs were divided into two equal groups (n = 10/each). In the first group, methenamine (150 mg/kg egg weight) was injected on the shell membrane, and in the second group (control group) phosphate-buffered salineas injected. Methenamine was inoculated at 96 and 120 hrafter incubation; 24 hrafter the last inoculation, the eggs were removed and the egg’s shell was incised. Then, the development of vascular network and vascular endothelial growth factor Aexpression was evaluated.
Results: Angiogenesis was significantly decreased after methenamine treatment. The indexes such as areas containing vessels, the vessels’ length, the percentage of angiogenesis developing areas, and vascular complexity in the treatment group receiving methenamine were significantly reduced compared to the control group. Vascular endothelial growth factor Aexpression was suppressed in the methenamine treated group.
Conclusion: According to the achieved results, it was defined that methenamine could have an inhibitory effect on the growth and development procedures of extraembryonic vasculature.

Keywords
Methenamine; Angiogenesis modulating agents; Vascular endothelial growth factor A; Extraembryonic membranes.