Research Article
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Investigation of Capsaicin-Induced Morphometric Changes, IGF-I and IGF-IR Expressions in Rat Ileum

Year 2024, Volume: 43 Issue: 2, 102 - 107, 31.12.2024
https://doi.org/10.30782/jrvm.1563880

Abstract

This study investigated the histomorphological changes in the ileum after capsaicin application and the expression of IGFI and its receptor IGFI-R, which play a role in regulating cellular growth, differentiation and apoptosis through endocrine, paracrine and autocrine effects. 21-day-old Sprague-Dawley rats were divided into 2 groups as the Control group and the Capsaicin-receiving treatment group. 0.5mg/kg Capsaicin was applied subcutaneously to the treatment group for 20 days. At the end of the experiment, the ileums were collected and the tissues were evaluated with immunohistochemistry (IGF-I, IGF-IR) and morphometric analyses. The parameters supporting digestion in the treatment groups, such as villus height, crypt depth, total mucosal thickness, villus/crypt ratio, and surface absorption area, increased statistically. In addition, an increase in the expression of IGF-I and IGF-IR was determined in the crypts and smooth muscle layer. However, no statistical significance was detected in the surface epithelium compared to the control group. The increase in histomorphological parameters and the increase in the expression of IGF-I and its receptor seen in the crypt glands where the cells are mitotically densest lead to the conclusion that capsaicin affects the mechanism of action of IGF-I and IGF-IR and that the treatment positively affects intestinal morphology by supporting nutrient absorption and utilization in the digestive system.

Project Number

TOVAG:104 O 372

References

  • 1. Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev. 2012;1:Cd008921.
  • 2. Srinivasan K. Biological activities of red pepper (Capsicum annuum) and its pungent principle Capsaicin :A Review. Crit Rev Food Sci Nutr. 2016;56:1488–1500.
  • 3. Hammer J., Vogelsang H. Characterization of sensations induced by capsaicin in the upper gastrointestinal tract. Neurogastroenterol Motil. 2007;19:279–287.
  • 4. Mozsik G., Vincze A., Szolcsanyi J. Four response stages of capsaicin-sensitive primary afferent neurons to capsaicin and its analog: Gastric acid secretion, gastric mucosal damage and protection. J Gastroenterol Hepatol. 2001;16:1093–1097.
  • 5. Lu M, Cao Y, Ho CT, Huang Q. Development of organogel-derived Capsaicin nanoemulsion with improved bioaccessibility and reduced gastric mucosa irritation. J Agric Food Chem. 2016;64:4735–4741.
  • 6. Lu M, Cao Y, Ho CT, Huang Q. The enhanced anti-obesity effect and reduced gastric mucosa irritation of capsaicin-loaded nanoemulsions. Food Funct. 2017;8:1803–1809.
  • 7. Han J, Zhang S, Liu X, Xiao C. Fabrication of capsaicin emulsions: Improving the stability of system and relieving the irritation to the gastrointestinal tract of rats. J Sci Food Agric. 2019;100:129–138.
  • 8. Tsukura Y, Mori M, Hirotani Y, et al. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007;30:1982–1986.
  • 9. Umeda K, Ikenouchi J, Katahira-Tayama S, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell. 2006;126:741–754.
  • 10. Drewes AM, Schipper KP, Dimcevski G, et al. Gut pain and hyperalgesia induced by capsaicin: A human experimental model. Pain. 2003;104:333–341.
  • 11. Van Avesaat M, Troost FJ, Westerterp-Plantenga MS, et al. Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones. Am J Clin Nutr. 2016;103:305–313.
  • 12. Van Wanrooij SJM, Wouters MM, Van Oudenhove L, et al. Sensitivity Testing in Irritable Bowel Syndrome With Rectal Capsaicin Stimulations: Role of TRPV1 Upregulation and Sensitization in Visceral Hypersensitivity? Am J Gastroenterol. 2014;109:99–109.
  • 13. Xiang Q, Tang X, Cui S, et al. Capsaicin, the Spicy Ingredient of Chili Peppers: Effects on Gastrointestinal Tract and Composition of Gut Microbiota at Various Dosages. Foods. 2022;25:686.
  • 14. Beattie J, Allan GJ, Lochrie JD, Flint DJ. Insulin-like growth factorbinding protein-5 (IGFBP-5): a critical member of the IGF axis. Biochem J. 2006;395:1–19.
  • 15. Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE. Molecular interactions of the IGF system. Cytokine Growth Factor Rev. 2005;16:421-439.
  • 16. Yesilbag D, Abdullahoglu E, Urkmez E, Acar A, Asmaz D, Kara M. Evaluation of the Effects of Different Natural Dietary Feed Additives on Performance and Intestinal Histomorphology in Quails. J Hellenic Vet Med Soc. 2022;73:4407–4416.
  • 17. Guler S, Asmaz D, Kayapunar NV, et al. Effects of dietary calcium, phosphorus and microbial phytase on intestinal morphologyin laying hens. Turk J Vet Anim Sci. 2022;46:2:14.
  • 18. Asmaz ED, Yesilbag D, Odabasi F, Zık B. Synergistic effect of feed additives on cell proliferation and morphology in quail (Coturnix coturnix Japonica) duodenum. J Hellenic Vet Med Soc. 2022;73:4575-4582.
  • 19. Özgüden-Akkoç CG, Asmaz ED, İlhan T, Zık B. Düşük doz kapsaicin uygulanan sıçanların ovaryumlarında TGF-Beta 1’in immunohistokimyasal yerleşimi. Erciyes Üniv Vet Fak Derg. 2018;15:238-246.
  • 19. Asmaz ED, Seyidoglu N. The prevention role of Spirulina platensis (Arthrospira platensis) on intestinal health. Food Sci Hum Wellness. 2022;11:1342–1346.
  • 20 Kwon Y. Estimation of dietary capsaicinoid exposure in Korea and assessment of its health effects. Nutrients. 2021;13:2461.
  • 21. Nair A., Morsy M.A., Jacob S. Dose translation between laboratory animals and human in preclinical and clinical phases of drug development. Drug Dev Res. 2018;79:373–382.
  • 22. Han J, Zhang S, Liu X, Xiao C. Fabrication of capsaicin emulsions: Improving the stability of system and relieving the irritation to the gastrointestinal tract of rats. J Sci Food Agric. 2019;100:129–138.
  • 23. Rashid MH, Inou M, Kondo S, Kawashıma T, Bakoshi S, Ueda H. Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain. J Pharmacol Exp Ther. 2003;304:940-8.
  • 24.Toth B, Gannett P. Carcinogenicity of lifelong administration of capsaicin of hot pepper in mice. In Vivo. 1992;6:59-63.
  • 25.Toth B, Rogan E, Walker B. Tumorigenicity and Mutagenicity Studies with Capsaicin of Hot Peppers. Anticancer Res. 1984;4:117-9.
  • 26. Anuras S, Christiansen J, TEmpleman D. Effect of Capsaicin on Electrical Slow Waves in the Isolated Rat Colon. Gut. 1977;18:666-669.
  • 27. Jensen-Jaorlim E, Gajdzik L, Haberl I. Hot Spices Influence Permeability of Human Intestinal Epithelial Monolayers. J Nutr. 1998;128: 577-81.
  • 28.Uchida M, Yano S, Watanabe K. The Role of Capsaicin-Sensitive Afferent Nerves in Protective Effect of Capsaicin Against Ethanol-Induced Gastric Lesions in Rats. Jpn J Pharmacol. 1991;55:279-822.
  • 29. Kuemmerle JF. Insulin-like growth factors in the gastrointestinal tract and liver. Endocrinol Metab Clin North Am. 2012;409-423.
  • 30 Qiu W, Leibowitz B, Zhang L, Yu J. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis. Oncogene. 2010;29:1622–1632.
  • 31. Ramocki NM, Wilkins HR, Magness ST, et al. Insulin receptor substrate-1 deficiency promotes apoptosis in the putative intestinal crypt stem cell region, limits Apcmin/+ tumors, and regulates Sox9. Endocrinology. 2008;149:261–267.
  • 32. Burrin DG, Wester TJ, Davis TA, Amick S, Heath JP. Orally administered IGF-I increases intestinal mucosal growth in formula-fed neonatal pigs. Am J Physiol. 1996;270:R1085–R1091.
  • 33. Potten CS, Owen G, Hewitt D, et al. Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Gut. 1995;36:864–873.
  • 34. Steeb CB, Trahair JF, Tomas FM, Read LC. Prolonged administration of IGF peptides enhances growth of gastrointestinal tissues in normal rats. Am J Physiol. 1994;266:G1090–G1098.

Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi

Year 2024, Volume: 43 Issue: 2, 102 - 107, 31.12.2024
https://doi.org/10.30782/jrvm.1563880

Abstract

Bu çalışma kapsaisin uygulaması sonrası ileumdaki histomorfolojik değişiklik ve endokrin, parakrin, otokrin etkiler yoluyla hücresel büyümeyi, farklılaşmayı ve apoptozu düzenlemede rol alan IGFI ve onun reseptörü olan IGFI-R’nün ifadesi araştırılmıştır. 21 günlük Sprague-Dawley sıçan Kontrol gurubu ve Kapsaisin alan tedavi grubu olarak 2’ye ayrıldı. Tedavi grubuna 20 gün boyunca deri altında 0,5mg/kg Kapsaisin uygulandı Deney sonunda ileumlar toplanarak dokular immünohistokimya (IGF-I-IGF-IR) ve morfometrik analizlerle değerlendirildi. Tedavi gruplarının sindirimi destekleyen parametrelerinden villus yüksekliği, kript derinliği, total mukozal kalınlığı, villus/kript oranı, yüzey emilim alanı istatistiki olarak arttı. Ayrıca kriptlerde ve düz kas tabakasında IGF-I ve IGFI-R’nün ifadesinde artış belirlendi. Ancak yüzey epitelinde kontrol grubuna göre herhangi bir istatistiki önem tespit edilmedi. Histomorfolojik parametrelerdeki artış ve hücrelerin mitotik olarak en yoğun olduğu kript bezlerinde görülen IGF-I ve reseptörünün ifadesinde artış Kapsaisinin IGF-I ve IGF-IR etki mekanizmasını etkilediği ve tedavinin sindirim sisteminde besin emilimini ve yararlanımını destekleyerek bağırsak morfolojisini olumlu yönde etkilediği sonucuna vardık.

Ethical Statement

Deney protokolleri Uludağ Üniversitesi Hayvan Bakım ve Kullanım Komitesi tarafından onaylandı ve Ulusal Sağlık Enstitüsü Laboratuvar Hayvanlarının Bakımı ve Kullanımı Kılavuzu'na (karar no: 08.06.2005/2) uygun olarak ilerlendi.

Supporting Institution

Bu çalışma TÜBİTAK-TOVAG (Türkiye Bilimsel ve Teknolojik Araştırma Kurumu) 104 O 372 numaralı projeden sağlanan bütçe ile finanse edilmiştir.

Project Number

TOVAG:104 O 372

Thanks

Bursa Uludağ Üniversitesi Veteriner Fakültesi Histoloji ve Embriyoloji Anabilim Dalı öğretim üyesi Prof. Dr. Berrin Zık’a çalışmanın yürültülmesinde verdiği sonsuz destek için teşekkürlerimi sunmayı bir borç bilirim.

References

  • 1. Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain management in rheumatoid arthritis. Cochrane Database Syst Rev. 2012;1:Cd008921.
  • 2. Srinivasan K. Biological activities of red pepper (Capsicum annuum) and its pungent principle Capsaicin :A Review. Crit Rev Food Sci Nutr. 2016;56:1488–1500.
  • 3. Hammer J., Vogelsang H. Characterization of sensations induced by capsaicin in the upper gastrointestinal tract. Neurogastroenterol Motil. 2007;19:279–287.
  • 4. Mozsik G., Vincze A., Szolcsanyi J. Four response stages of capsaicin-sensitive primary afferent neurons to capsaicin and its analog: Gastric acid secretion, gastric mucosal damage and protection. J Gastroenterol Hepatol. 2001;16:1093–1097.
  • 5. Lu M, Cao Y, Ho CT, Huang Q. Development of organogel-derived Capsaicin nanoemulsion with improved bioaccessibility and reduced gastric mucosa irritation. J Agric Food Chem. 2016;64:4735–4741.
  • 6. Lu M, Cao Y, Ho CT, Huang Q. The enhanced anti-obesity effect and reduced gastric mucosa irritation of capsaicin-loaded nanoemulsions. Food Funct. 2017;8:1803–1809.
  • 7. Han J, Zhang S, Liu X, Xiao C. Fabrication of capsaicin emulsions: Improving the stability of system and relieving the irritation to the gastrointestinal tract of rats. J Sci Food Agric. 2019;100:129–138.
  • 8. Tsukura Y, Mori M, Hirotani Y, et al. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007;30:1982–1986.
  • 9. Umeda K, Ikenouchi J, Katahira-Tayama S, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell. 2006;126:741–754.
  • 10. Drewes AM, Schipper KP, Dimcevski G, et al. Gut pain and hyperalgesia induced by capsaicin: A human experimental model. Pain. 2003;104:333–341.
  • 11. Van Avesaat M, Troost FJ, Westerterp-Plantenga MS, et al. Capsaicin-induced satiety is associated with gastrointestinal distress but not with the release of satiety hormones. Am J Clin Nutr. 2016;103:305–313.
  • 12. Van Wanrooij SJM, Wouters MM, Van Oudenhove L, et al. Sensitivity Testing in Irritable Bowel Syndrome With Rectal Capsaicin Stimulations: Role of TRPV1 Upregulation and Sensitization in Visceral Hypersensitivity? Am J Gastroenterol. 2014;109:99–109.
  • 13. Xiang Q, Tang X, Cui S, et al. Capsaicin, the Spicy Ingredient of Chili Peppers: Effects on Gastrointestinal Tract and Composition of Gut Microbiota at Various Dosages. Foods. 2022;25:686.
  • 14. Beattie J, Allan GJ, Lochrie JD, Flint DJ. Insulin-like growth factorbinding protein-5 (IGFBP-5): a critical member of the IGF axis. Biochem J. 2006;395:1–19.
  • 15. Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE. Molecular interactions of the IGF system. Cytokine Growth Factor Rev. 2005;16:421-439.
  • 16. Yesilbag D, Abdullahoglu E, Urkmez E, Acar A, Asmaz D, Kara M. Evaluation of the Effects of Different Natural Dietary Feed Additives on Performance and Intestinal Histomorphology in Quails. J Hellenic Vet Med Soc. 2022;73:4407–4416.
  • 17. Guler S, Asmaz D, Kayapunar NV, et al. Effects of dietary calcium, phosphorus and microbial phytase on intestinal morphologyin laying hens. Turk J Vet Anim Sci. 2022;46:2:14.
  • 18. Asmaz ED, Yesilbag D, Odabasi F, Zık B. Synergistic effect of feed additives on cell proliferation and morphology in quail (Coturnix coturnix Japonica) duodenum. J Hellenic Vet Med Soc. 2022;73:4575-4582.
  • 19. Özgüden-Akkoç CG, Asmaz ED, İlhan T, Zık B. Düşük doz kapsaicin uygulanan sıçanların ovaryumlarında TGF-Beta 1’in immunohistokimyasal yerleşimi. Erciyes Üniv Vet Fak Derg. 2018;15:238-246.
  • 19. Asmaz ED, Seyidoglu N. The prevention role of Spirulina platensis (Arthrospira platensis) on intestinal health. Food Sci Hum Wellness. 2022;11:1342–1346.
  • 20 Kwon Y. Estimation of dietary capsaicinoid exposure in Korea and assessment of its health effects. Nutrients. 2021;13:2461.
  • 21. Nair A., Morsy M.A., Jacob S. Dose translation between laboratory animals and human in preclinical and clinical phases of drug development. Drug Dev Res. 2018;79:373–382.
  • 22. Han J, Zhang S, Liu X, Xiao C. Fabrication of capsaicin emulsions: Improving the stability of system and relieving the irritation to the gastrointestinal tract of rats. J Sci Food Agric. 2019;100:129–138.
  • 23. Rashid MH, Inou M, Kondo S, Kawashıma T, Bakoshi S, Ueda H. Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain. J Pharmacol Exp Ther. 2003;304:940-8.
  • 24.Toth B, Gannett P. Carcinogenicity of lifelong administration of capsaicin of hot pepper in mice. In Vivo. 1992;6:59-63.
  • 25.Toth B, Rogan E, Walker B. Tumorigenicity and Mutagenicity Studies with Capsaicin of Hot Peppers. Anticancer Res. 1984;4:117-9.
  • 26. Anuras S, Christiansen J, TEmpleman D. Effect of Capsaicin on Electrical Slow Waves in the Isolated Rat Colon. Gut. 1977;18:666-669.
  • 27. Jensen-Jaorlim E, Gajdzik L, Haberl I. Hot Spices Influence Permeability of Human Intestinal Epithelial Monolayers. J Nutr. 1998;128: 577-81.
  • 28.Uchida M, Yano S, Watanabe K. The Role of Capsaicin-Sensitive Afferent Nerves in Protective Effect of Capsaicin Against Ethanol-Induced Gastric Lesions in Rats. Jpn J Pharmacol. 1991;55:279-822.
  • 29. Kuemmerle JF. Insulin-like growth factors in the gastrointestinal tract and liver. Endocrinol Metab Clin North Am. 2012;409-423.
  • 30 Qiu W, Leibowitz B, Zhang L, Yu J. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis. Oncogene. 2010;29:1622–1632.
  • 31. Ramocki NM, Wilkins HR, Magness ST, et al. Insulin receptor substrate-1 deficiency promotes apoptosis in the putative intestinal crypt stem cell region, limits Apcmin/+ tumors, and regulates Sox9. Endocrinology. 2008;149:261–267.
  • 32. Burrin DG, Wester TJ, Davis TA, Amick S, Heath JP. Orally administered IGF-I increases intestinal mucosal growth in formula-fed neonatal pigs. Am J Physiol. 1996;270:R1085–R1091.
  • 33. Potten CS, Owen G, Hewitt D, et al. Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Gut. 1995;36:864–873.
  • 34. Steeb CB, Trahair JF, Tomas FM, Read LC. Prolonged administration of IGF peptides enhances growth of gastrointestinal tissues in normal rats. Am J Physiol. 1994;266:G1090–G1098.
There are 35 citations in total.

Details

Primary Language Turkish
Subjects Veterinary Sciences (Other)
Journal Section Research Articles
Authors

Ender Deniz Asmaz 0000-0001-6468-8535

Project Number TOVAG:104 O 372
Publication Date December 31, 2024
Submission Date October 9, 2024
Acceptance Date November 27, 2024
Published in Issue Year 2024 Volume: 43 Issue: 2

Cite

APA Asmaz, E. D. (2024). Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi. Journal of Research in Veterinary Medicine, 43(2), 102-107. https://doi.org/10.30782/jrvm.1563880
AMA Asmaz ED. Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi. J Res Vet Med. December 2024;43(2):102-107. doi:10.30782/jrvm.1563880
Chicago Asmaz, Ender Deniz. “Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I Ve IGF-IR Ekspresyonlarının İncelenmesi”. Journal of Research in Veterinary Medicine 43, no. 2 (December 2024): 102-7. https://doi.org/10.30782/jrvm.1563880.
EndNote Asmaz ED (December 1, 2024) Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi. Journal of Research in Veterinary Medicine 43 2 102–107.
IEEE E. D. Asmaz, “Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi”, J Res Vet Med, vol. 43, no. 2, pp. 102–107, 2024, doi: 10.30782/jrvm.1563880.
ISNAD Asmaz, Ender Deniz. “Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I Ve IGF-IR Ekspresyonlarının İncelenmesi”. Journal of Research in Veterinary Medicine 43/2 (December 2024), 102-107. https://doi.org/10.30782/jrvm.1563880.
JAMA Asmaz ED. Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi. J Res Vet Med. 2024;43:102–107.
MLA Asmaz, Ender Deniz. “Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I Ve IGF-IR Ekspresyonlarının İncelenmesi”. Journal of Research in Veterinary Medicine, vol. 43, no. 2, 2024, pp. 102-7, doi:10.30782/jrvm.1563880.
Vancouver Asmaz ED. Sıçan İleumunda Kapsaisinin Neden Olduğu Morfometrik Değişikliklerin, IGF-I ve IGF-IR Ekspresyonlarının İncelenmesi. J Res Vet Med. 2024;43(2):102-7.