Farklı Gelişim Dönemlerinde Capsaicin Uygulanan Ratların Uteruslarında Plazma Hücre Sayıları ve CD138 Ekspresyonunun Değerlendirilmesi

Öz

Acı biberin aktif bileşeni olan capsaicin organizmada analjezik, antiinflamatuar, antimikrobiyal ve kemopreventif etkiler gösterebilmektedir. Capsaicinin bağışıklık sistemi üzerindeki etkilerinin dokuya özgü biyolojik ortam ve gelişimsel dönemle ilişkili olarak değişebileceği bildirilmektedir. Bu çalışma, farklı gelişim dönemlerinde uygulanan capsaicinin rat uterusunda plazma hücre sayıları ve CD138 ekspresyon düzeyleri üzerindeki etkilerini değerlendirmek amacıyla yapılmıştır. Altmış dişi Sprague-Dawley rat (21 günlük), puberte ve erişkin olarak rastgele 2 gruba ayrıldı ve sırasıyla 42 ve 70 günlük olana kadar ilgili deney koşullarına maruz bırakıldı. Her grup ayrıca kontrol, taşıyıcı solüsyon ve capsaicin olarak üç alt gruba ayrıldı. Deney süresi sonunda uterus dokularının histolojik yapısı değerlendirildi. Plazma hücreleri Metil Green–Pyronin boyama ile CD138 ekspresyonu ise immünohistokimyasal yöntemle analiz edildi. Histokimyasal değerlendirmede puberte döneminde taşıyıcı solüsyon grubunun plazma hücre sayısının kontrol grubuna göre daha düşük olduğu belirlendi, erişkin dönemde ise gruplar arasında anlamlı fark saptanmadı. Bununla birlikte taşıyıcı solüsyon ve capsaicin gruplarında yaşla birlikte plazma hücre sayısında artış gözlenirken kontrol grubunda yaşa bağlı değişiklik tespit edilmedi. İmmünohistokimyasal analizlerde her iki gelişimsel dönem içerisinde gruplar arası fark bulunmamakla birlikte capsaicin grubunda erişkin dönemde puberte dönemine göre CD138 pozitif hücre sayısında anlamlı artış belirlendi. Sonuç olarak, capsaicinin uterin plazma hücre dinamikleri üzerindeki etkisinin gelişimsel döneme bağlı olarak değişebileceği ve değerlendirmede kullanılan yöntemin sonuçların yorumlanmasında belirleyici olabileceği kanaatine varılmıştır.

Anahtar Kelimeler

• Capsaicin
• CD138
• Plazma Hücresi
• Uterus

Evaluation of Plasma Cell Counts and CD138 Expression in the Rat Uterus Following Capsaicin Treatment at Different Developmental Stages

Öz

Capsaicin, the bioactive component of chili peppers, has been reported to exert analgesic, anti-inflammatory, antimicrobial, and chemopreventive effects. The immunomodulatory properties of capsaicin are suggested to vary depending on the tissue microenvironment and developmental stage. The study aimed to evaluate the effects of capsaicin administered at different developmental periods on plasma cell counts and CD138 expression levels in the rat uterus. Sixty female Sprague–Dawley rats (21 days) were randomly assigned to pubertal and adult groups and exposed to the respective experimental conditions until reaching 42 or 70 days of age. Each group was further subdivided into control, vehicle, and capsaicin treated groups. At the end of the experimental period, uterine histological architecture was assessed. Plasma cells were identified by Methyl Green–Pyronin staining, and CD138 expression was analysed immunohistochemically. Histochemical evaluation revealed a significantly lower number of plasma cells in the vehicle group compared with the control group during puberty, whereas no significant differences were observed among groups in adulthood. Notably, plasma cell counts increased with age in the vehicle and capsaicin groups, while no age-related change was detected in the control group. Immunohistochemical analysis revealed no significant differences among treatment groups within each developmental stage; however, a significant increase in CD138-positive cells was observed in the adult capsaicin group compared with the pubertal capsaicin group. In conclusion, the effects of capsaicin on uterine plasma cell dynamics appear to be influenced by developmental stage, and the method used for evaluation may affect the interpretation of immune-related changes.

Anahtar Kelimeler

• Capsaicin
• CD138
• Plasma Cell
• Uterus

Kaynakça

1. Bancroft, J., & Cook, H. (1984). Manual of Histological Techniques Churchill Livingstone. New York, 18-25.
2. Barceloux, D. G. (2009). Pepper and capsaicin (Capsicum and Piper species). Disease-a-Month, 55(6), 380-390.
3. Barnett, J. B. (1981). Immunosuppressive effects of tween 80 on mice. International Archives of Allergy and Immunology, 66(2), 229-232.
4. Blazheva, S., Pachkova, S., Bodurska, T., Ivanov, P., Blazhev, A., Lukanov, T., & Konova, E. (2024). Unlocking the uterine code: microbiota, immune cells, and therapy for recurrent reproductive failure. Microorganisms, 12(3), 547.
5. Chen, Y.-q., Fang, R.-l., Luo, Y.-n., & Luo, C.-q. (2016). Analysis of the diagnostic value of CD138 for chronic endometritis, the risk factors for the pathogenesis of chronic endometritis and the effect of chronic endometritis on pregnancy: a cohort study. BMC women's health, 16(1), 60.
6. Cicinelli, E., Haimovich, S., De Ziegler, D., Raz, N., Ben-Tzur, D., Andrisani, A., Ambrosini, G., Picardi, N., Cataldo, V., & Balzani, M. (2022). MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining. Journal of assisted reproduction and genetics, 39(1), 219-226.
7. Crossmon, G. (1937). A modification of Mallory's connective tissue stain with a discussion of the principles involved. The Anatomical Record, 69(1), 33-38.
8. De, A. K., & Ghosh, J. J. (1989). Short‐and long‐term effects of capsaicin on the pulmonary anti‐oxidant enzyme system in rats. Phytotherapy Research, 3(5), 184-187.

9. Dumancic, S., Bakotin Jakovac, M., Mimica, M. D., Zekic Tomas, S., & Marusic, J. (2025). CD56-positive NK cells and CD138-positive plasma cells in basal decidua of term placentas in singleton pregnancies after assisted reproductive technology treatment of endometriosis-related infertility. Life, 15(2), 240.
10. Ekemen, S., Comunoglu, C., Kayhan, C. K., Bilir, E., Cavusoglu, I., Etiler, N., Bilgi, S., Ince, U., Coban, C., & Erden, H. F. (2023). Endometrial staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) improve diagnosis and clinical pregnancy outcomes in unexplained infertility and recurrent IVF failures: Standardization of diagnosis with digital pathology. Diagnostics, 13(9), 1557.
11. Ertuğrul, T., Tütüncü, Ş., Delice, N., & Özdemir, B. (2024). Histochemical and immunohistochemical investigation of the number and localization of mast cells in the feline tongue. Anatomia, Histologia, Embryologia, 53(4), e13069.
12. Holder, M. K., Peters, N. V., Whylings, J., Fields, C. T., Gewirtz, A. T., Chassaing, B., & de Vries, G. J. (2019). Dietary emulsifiers consumption alters anxiety-like and social-related behaviors in mice in a sex-dependent manner. Scientific Reports, 9(1), 172.
13. Li, Y., Xu, S., Yu, S., Huang, C., Lin, S., Chen, W., Mo, M., Lian, R., Diao, L., & Ding, L. (2021). Diagnosis of chronic endometritis: How many CD138+ cells/HPF in endometrial stroma affect pregnancy outcome of infertile women? American journal of reproductive immunology, 85(5), e13369.
14. Lightman, S. M., Utley, A., & Lee, K. P. (2019). Survival of long-lived plasma cells (LLPC): piecing together the puzzle. Frontiers in immunology, 10, 965.
15. Luna, L. G. (1968). Manual of histologic staining methods of the Armed Forces Institute of Pathology. In Manual of histologic staining methods of the Armed Forces Institute of Pathology (pp. xii, 258-xii, 258).
16. Ma, K., Wang, X., Shi, X., Lin, X., Xiao, F., Ma, X., Liu, D., & Lu, L. (2020). The expanding functional diversity of plasma cells in immunity and inflammation. Cellular & Molecular Immunology, 17(4), 421-422.
17. McQueen, D. B., Maniar, K. P., Hutchinson, A., Confino, R., Bernardi, L., & Pavone, M. E. (2021). Redefining chronic endometritis: the importance of endometrial stromal changes. Fertility and sterility, 116(3), 855-861.
18. Messina, A., Libretti, A., Giovannini, I., Leo, L., Remorgida, V., Masturzo, B., & Tinelli, R. (2025). Role of CD138+ Plasma Cells and Natural Killer Cells in Couple Infertility: A Review. Biomedicines, 13(9), 2248.
19. Mor, G., & Cardenas, I. (2010). The immune system in pregnancy: a unique complexity. American Journal of Reproductive Immunology, 63(6), 425-433.
20. Patowary, P., Pathak, M. P., Zaman, K., Raju, P., & Chattopadhyay, P. (2017). Research progress of capsaicin responses to various pharmacological challenges. Biomedicine & Pharmacotherapy, 96, 1501-1512.
21. Picut, C. A., Remick, A. K., Asakawa, M. G., Simons, M. L., & Parker, G. A. (2014). Histologic features of prepubertal and pubertal reproductive development in female Sprague-Dawley rats. Toxicologic pathology, 42(2), 403-413.
22. Robertson, S. A. (2005). Seminal plasma and male factor signalling in the female reproductive tract. Cell and tissue research, 322(1), 43-52.
23. Ryan, E., Tolani, A. T., Zhang, J., Cruz, G. I., Folkins, A. K., & Lathi, R. B. (2022). The menstrual cycle phase impacts the detection of plasma cells and the diagnosis of chronic endometritis in endometrial biopsy specimens. Fertility and sterility, 118(4), 787-794.
24. Santoro, A., Travaglino, A., Inzani, F., Angelico, G., Raffone, A., Maruotti, G. M., Straccia, P., Arciuolo, D., Castri, F., & D’Alessandris, N. (2023). The role of plasma cells as a marker of chronic endometritis: a systematic review and meta-analysis. Biomedicines, 11(6), 1714.
25. Stanisz, A. M., Befus, D., & Bienenstock, J. (1986). Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. Journal of immunology (Baltimore, Md.: 1950), 136(1), 152-156.
26. Stewart, C. A., Fisher, S. J., Wang, Y., Stewart, M. D., Hewitt, S. C., Rodriguez, K. F., Korach, K. S., & Behringer, R. R. (2011). Uterine gland formation in mice is a continuous process, requiring the ovary after puberty, but not after parturition. Biology of reproduction, 85(5), 954-964.
27. Takimoto, K., Yamada, H., Shimada, S., Fukushi, Y., & Wada, S. (2023). Chronic endometritis and uterine endometrium microbiota in recurrent implantation failure and recurrent pregnancy loss. Biomedicines, 11(9), 2391.
28. Traurig, H. H., Papka, R. E., & Rush, M. E. (1988). Effects of capsaicin on reproductive function in the female rat: Role of peptide-containing primary afferent nerves innervating the uterine cervix in the neuroendocrine copulatory response. Cell and Tissue Research, 253(3), 573–581.
29. Tutuncu, S., & Ertugrul, T. (2020). Mast cell density and expression of tryptase, IFN-γ, TNF-α in capsaicin-treated rat uterus. Journal of Applied Biological Sciences, 16(1), 169-181.
30. Viveros-Paredes, J., Puebla-Pérez, A., Gutiérrez-Coronado, O., Macías-Lamas, A., Hernández-Flores, G., Ortiz-Lazareno, P., Bravo-Cuéllar, A., & Villaseñor-García, M. (2021). Capsaicin attenuates immunosuppression induced by chronic stress in BALB/C mice. International Immunopharmacology, 93, 107341.
31. Wang, Y., Dong, X., Qu, Z., Peng, K., Sun, X., & Chen, R. (2020). Correlation between peripheral blood neutrophil-lymphocyte ratio and CD34 expression in prostate cancer. BMC cancer, 20(1), 900.
32. Xu, Q., Sun, L., Zhang, W., Wu, H., Jiao, C., Xu, L., Qian, X., Yao, H., Chen, Q., Xu, F., Fu, F., Wang, L., & Chen, X. (2021). A novel visceral pain model of uterine cervix inflammation in rat. European Journal of Pharmacology, 900, 174080.
33. Yu, R., Park, J., Kurata, T., & Erickson, K. (1998). Modulation of select immune responses by dietary capsaicin. International Journal for Vitamin and Nutrition research. Internationale Zeitschrift fur Vitamin-und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition, 68(2), 114-119.
34. Zhang, W., Zhang, Y., Fan, J., Feng, Z., & Song, X. (2024). Pharmacological activity of capsaicin: Mechanisms and controversies. Molecular Medicine Reports, 29(3), 38.
35. Zhaohui, Z., Yugui, C., Yuanming, Z., Xuesong, W., Xiaobing, J., Zhice, X., Guipeng, D., Qianle, T., & Yue, J. (2007). Effect of acupuncture on pubertal development of rats and rabbits at different developmental stages. Neuropeptides, 41(4), 249-261.