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Tavakkoli, H., Imani, M., Mohammad Rahchamani, S., & Rezvani, M. (2020). The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods. International Journal of Reproductive BioMedicine (IJRM), 13(8), 579–590. https://doi.org/10.18502/ijrm.v13i8.7497
https://doi.org/10.18502/ijrm.v13i8.7497
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authors
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Hadi Tavakkoli
Hadi Tavakkoli
Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
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Masoud Imani
Masoud Imani
Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
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Seyyed Mohammad Rahchamani
Seyyed Mohammad Rahchamani
Department of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
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Mohsen Rezvani
Mohsen Rezvani
Department of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
Published Date
- Aug 19, 2020
The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods
Abstract
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 saline as injected. Methenamine was inoculated at 96 and 120 hr after incubation; 24 hr after 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 A expression 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 A expression 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.
Key words: Methenamine, Angiogenesis modulating agents, Vascular endothelial growth factor A, Extraembryonic membranes.
References
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[2] Vainrub B, Musher DM. Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection. Antimicrob Agents Chemother 1977; 12: 625–629.
[3] Gerstein AR, Okun R, Gonick HC, Wilner HI, Kleeman CR, Maxwell MH. The prolonged use of methenaminehippurate in the treatment of chronic urinary tract infection. J Urol 1968; 100: 767–771.
[4] Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182–1186.
[5] Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671–674.
[6] Strömblad S, Cheresh DA. Integrins, angiogenesis and vascular cell survival. Chem Biol 1996; 3: 881– 885.
[7] Kim S, Bell K, Mousa SA, Varner JA. Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. Am J Pathol 2000; 156: 1345–1362.
[8] Demir R, Kaufmann P, Castellucci M, Erbengi T, Kotowski A. Fetal vasculogenesis and angiogenesis in human placental villi. Acta Anat (Basel) 1989; 136: 190–203.
[9] teVelde EA, Exalto N, Hesseling P, van der Linden HC. First trimester development of human chorionic villous 13vascularization studied with CD34 immunohistochemistry. Hum Reprod 1997; 12: 1577–1581.
[10] Meegdes BH, Ingenhoes R, Peeters LL, Exalto N. Early pregnancy wastage: relationship between chorionic vascularization and embryonic development. Fertil Steril 1988; 49: 216–220.
[11] Zygmunt M, Herr F, Münstedt K, Lang U, Liang OD. Angiogenesis and vasculogenesis in pregnancy. European Journal of Obstetrics Gynecology and Reproductive Biology 2003; 110: S10–S18.
[12] Vargesson N. Thalidomide-induced limb defects: resolving a 50-year-old puzzle. Bioessays 2009; 31: 1327–1336.
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[14] Tufan AC, Satiroglu-Tufan NL. The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents. Curr Cancer Drug Targets 2005; 5: 249–266.
[15] Gheorghescu AK, Tywoniuk B, Duess J, Buchete NV, Thompson J. Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGFR2. Toxicol Appl Pharmacol 2015; 289: 79–88.
[16] Khosravi A, Sharifi I, Tavakkoli H, Keyhani AR, Afgar A, Salari Z, et al. Vascular apoptosis associated with meglumine antimoniate: In vivo investigation of a chick embryo model. Biochem Biophys Res Commun 2018; 505: 794–800.
[17] Oosterbaan AM, Steegers EA, Ursem NT. The effects of homocysteine and folic acid on angiogenesis and VEGF expression during chicken vascular development. Microvasc Res 2012; 83: 98–104.
[18] Blacher S, Devy L, Hlushchuk R, Larger E, Lamandé N, Burri P, et al. Quantification of angiogenesis in the chicken chorioallantoic membrane (CAM). Image Anal Stereol 2005; 24: 169–180.
[19] Seidlitz E, Korbie D, Marien L, Richardson M, Singh G. Quantification of anti-angiogenesis using the capillaries of the chick chorioallantoic membrane demonstrates that the effect of human angiostatin is age-dependent. Microvasc Res 2004; 67: 105–116.
[20] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 2010; 31: 455–461.
[21] Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th Ed. Baltimore: Williams & Wilkins; 1998: 2471–2472. [22] Reynolds LP, Killilea SD, Redmer DA. Angiogenesis in the female reproductive system. FASEB J 1992; 6: 886–892.
[23] Torry RJ, Rongish BJ. Angiogenesis in the uterus: potential regulation and relation to tumor angiogenesis. Am J Reprod Immunol 1992; 27: 171–179.
[24] Asan E, Kaymaz FF, Cakar AN, Dagdeviren A, Beksac MS. Vasculogenesis in early human placental villi: an ultrastructural study. Ann Anat 1999; 181: 549–554.
[25] Dekker GA, Sibai BM. Etiology and pathogenesis of pre-eclampsia: current concepts. Am J Obstet Gynecol 1998; 179: 1359–1375.
[26] Macara L, Kingdom JC, Kaufmann P, Kohnen G, Hair J, More IA, et al. Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms. Placenta 1996; 17: 37–48.
[27] Bahar AA, Liu Z, Garafalo M, Kallenbach N, Ren D. Controlling persister and biofilm cells of gramnegative bacteria with a new 1,3,5-triazine derivative. Pharmaceuticals (Basel) 2015; 8: 696–710.
[28] Mibu N, Yokomizo K, Aki H, Ota N, Fujii H, Yuzuriha A, et al. Synthesis and antiviral evaluation of some C(3)- Symmetrical trialkoxy-substituted 1,3,5-triazines and their molecular geometry. Chem Pharm Bull (Tokyo) 2015; 63: 935–944.
[29] Zacharie B, Abbott SD, Bienvenu JF, Cameron AD, Cloutier J, Duceppe JS, et al. 2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases. J Med Chem 2010; 53: 1138–1145.
[30] Cascioferro S, Parrino B, Spano V, Carbone A, Montalbano A, Barraja P, et al. 1,3,5-Triazines: A promising scaffold for anticancer drugs development. Eur J Med Chem 2017; 142: 523– 549.
[31] Baindur N, Chadha N, Brandt BM, Asgari D, Patch RJ, Schalk-Hihi C, et al. 2-Hydroxy-4,6-diamino-[1,3,5] triazines: a novel class of VEGFR2 (KDR) tyrosine kinase inhibitors. J Med Chem 2005; 48: 1717–1720.
[32] Nozaki S, Maeda M, Tsuda H, Sledge GW Jr. Inhibition of breast cancer regrowth and pulmonary metastasis in nude mice by anti-gastric ulcer agent, irsogladine. Breast Cancer Res Treat 2004; 83: 195–199.
[33] Dao P, Jarray R, Le Coq J, Lietha D, Loukaci A, Lepelletier Y, et al. Synthesis of novel diarylamino- 1,3,5- triazine derivatives as FAK inhibitors with anti-angiogenic activity. Bioorg Med Chem Lett 2013; 23: 4552–4556.
[34] Zerin T, Kim JS, Gil HW, Song HY, HongSY. Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells. Cell Biol Toxicol 2015; 31: 261–272.
[35] Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435–439.
[2] Vainrub B, Musher DM. Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection. Antimicrob Agents Chemother 1977; 12: 625–629.
[3] Gerstein AR, Okun R, Gonick HC, Wilner HI, Kleeman CR, Maxwell MH. The prolonged use of methenaminehippurate in the treatment of chronic urinary tract infection. J Urol 1968; 100: 767–771.
[4] Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182–1186.
[5] Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671–674.
[6] Strömblad S, Cheresh DA. Integrins, angiogenesis and vascular cell survival. Chem Biol 1996; 3: 881– 885.
[7] Kim S, Bell K, Mousa SA, Varner JA. Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. Am J Pathol 2000; 156: 1345–1362.
[8] Demir R, Kaufmann P, Castellucci M, Erbengi T, Kotowski A. Fetal vasculogenesis and angiogenesis in human placental villi. Acta Anat (Basel) 1989; 136: 190–203.
[9] teVelde EA, Exalto N, Hesseling P, van der Linden HC. First trimester development of human chorionic villous 13vascularization studied with CD34 immunohistochemistry. Hum Reprod 1997; 12: 1577–1581.
[10] Meegdes BH, Ingenhoes R, Peeters LL, Exalto N. Early pregnancy wastage: relationship between chorionic vascularization and embryonic development. Fertil Steril 1988; 49: 216–220.
[11] Zygmunt M, Herr F, Münstedt K, Lang U, Liang OD. Angiogenesis and vasculogenesis in pregnancy. European Journal of Obstetrics Gynecology and Reproductive Biology 2003; 110: S10–S18.
[12] Vargesson N. Thalidomide-induced limb defects: resolving a 50-year-old puzzle. Bioessays 2009; 31: 1327–1336.
[13] Porter RS. Merck Manual’s Online Medical Library. Whitehouse Station: available at: http://www.merck. com/mmhe/index.html.
[14] Tufan AC, Satiroglu-Tufan NL. The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents. Curr Cancer Drug Targets 2005; 5: 249–266.
[15] Gheorghescu AK, Tywoniuk B, Duess J, Buchete NV, Thompson J. Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGFR2. Toxicol Appl Pharmacol 2015; 289: 79–88.
[16] Khosravi A, Sharifi I, Tavakkoli H, Keyhani AR, Afgar A, Salari Z, et al. Vascular apoptosis associated with meglumine antimoniate: In vivo investigation of a chick embryo model. Biochem Biophys Res Commun 2018; 505: 794–800.
[17] Oosterbaan AM, Steegers EA, Ursem NT. The effects of homocysteine and folic acid on angiogenesis and VEGF expression during chicken vascular development. Microvasc Res 2012; 83: 98–104.
[18] Blacher S, Devy L, Hlushchuk R, Larger E, Lamandé N, Burri P, et al. Quantification of angiogenesis in the chicken chorioallantoic membrane (CAM). Image Anal Stereol 2005; 24: 169–180.
[19] Seidlitz E, Korbie D, Marien L, Richardson M, Singh G. Quantification of anti-angiogenesis using the capillaries of the chick chorioallantoic membrane demonstrates that the effect of human angiostatin is age-dependent. Microvasc Res 2004; 67: 105–116.
[20] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 2010; 31: 455–461.
[21] Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 5th Ed. Baltimore: Williams & Wilkins; 1998: 2471–2472. [22] Reynolds LP, Killilea SD, Redmer DA. Angiogenesis in the female reproductive system. FASEB J 1992; 6: 886–892.
[23] Torry RJ, Rongish BJ. Angiogenesis in the uterus: potential regulation and relation to tumor angiogenesis. Am J Reprod Immunol 1992; 27: 171–179.
[24] Asan E, Kaymaz FF, Cakar AN, Dagdeviren A, Beksac MS. Vasculogenesis in early human placental villi: an ultrastructural study. Ann Anat 1999; 181: 549–554.
[25] Dekker GA, Sibai BM. Etiology and pathogenesis of pre-eclampsia: current concepts. Am J Obstet Gynecol 1998; 179: 1359–1375.
[26] Macara L, Kingdom JC, Kaufmann P, Kohnen G, Hair J, More IA, et al. Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms. Placenta 1996; 17: 37–48.
[27] Bahar AA, Liu Z, Garafalo M, Kallenbach N, Ren D. Controlling persister and biofilm cells of gramnegative bacteria with a new 1,3,5-triazine derivative. Pharmaceuticals (Basel) 2015; 8: 696–710.
[28] Mibu N, Yokomizo K, Aki H, Ota N, Fujii H, Yuzuriha A, et al. Synthesis and antiviral evaluation of some C(3)- Symmetrical trialkoxy-substituted 1,3,5-triazines and their molecular geometry. Chem Pharm Bull (Tokyo) 2015; 63: 935–944.
[29] Zacharie B, Abbott SD, Bienvenu JF, Cameron AD, Cloutier J, Duceppe JS, et al. 2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases. J Med Chem 2010; 53: 1138–1145.
[30] Cascioferro S, Parrino B, Spano V, Carbone A, Montalbano A, Barraja P, et al. 1,3,5-Triazines: A promising scaffold for anticancer drugs development. Eur J Med Chem 2017; 142: 523– 549.
[31] Baindur N, Chadha N, Brandt BM, Asgari D, Patch RJ, Schalk-Hihi C, et al. 2-Hydroxy-4,6-diamino-[1,3,5] triazines: a novel class of VEGFR2 (KDR) tyrosine kinase inhibitors. J Med Chem 2005; 48: 1717–1720.
[32] Nozaki S, Maeda M, Tsuda H, Sledge GW Jr. Inhibition of breast cancer regrowth and pulmonary metastasis in nude mice by anti-gastric ulcer agent, irsogladine. Breast Cancer Res Treat 2004; 83: 195–199.
[33] Dao P, Jarray R, Le Coq J, Lietha D, Loukaci A, Lepelletier Y, et al. Synthesis of novel diarylamino- 1,3,5- triazine derivatives as FAK inhibitors with anti-angiogenic activity. Bioorg Med Chem Lett 2013; 23: 4552–4556.
[34] Zerin T, Kim JS, Gil HW, Song HY, HongSY. Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells. Cell Biol Toxicol 2015; 31: 261–272.
[35] Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435–439.