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Bağırsakta bağırır: Atopik dermatitli köpeklerde ‘bağırsak-beyin-deri ekseninde’ fekal intestinal alkalen fosfataz aktivitesinin ve çinko seviyelerinin ölçümü

Yıl 2025, Cilt: 7 Sayı: 2, 43 - 47, 29.12.2025
https://doi.org/10.51755/turkvetj.1780858

Öz

Gastrointestinal fizyolojide ve hastalıklarda kritik rolde olan izoenzim grubuna ait biyobelirtec olan fekal intestinal alkalen fosfataz’ın (F-IAP), beyin-bağırsak-deri ekseninde tanısal manada etkin olup olmadığının belirlenmesi hipotezinden yola çıkılarak gerçekleştirilen bu çalışma çift-kör, randomize, prospektif olarak planlanmıştır. Bu çalışmada bağırsak-beyin-deri ekseni odaklı değerlendirmede, aynı çalışma ekibinin önceki birikimleri, deneyimler ve çalışmaları bir adım öteye taşınarak atopik dermatitli köpeklerde alanımızda ilk olarak F-IAP aktivitesindeki değişimin, i) yeni bir gastroentero-dermatolojik sağlık biyobelirteci potansiyelini taşıyıp taşımayacağının belirlenmesi, ii) çinko seviyeleri ile olan ilişkisinin değerlendirilmesi, iii) intestinal mukoza koruyucu etkisinin bu hastalık aktivitesine ilişkin olarak azalıp azalmadığının belirlenmesi amaçlanmıştır. Çalışma kapsamına alınan n=14 atopik dermatitli ve karşılaştırmalı n=12 sağlıklı köpekte F-IAP ve serum çinko seviyeleri ölçüldü. Atopik dermatitli köpeklerde ortalama F-IAP değeri 13,8 IU/L iken sağlıklı kontrol grubunda 56,8 IU/L olarak ölçüldü (P = 0,0001). Benzer şekilde, serum çinko düzeyleri de atopik dermatitli bireylerde anlamlı derecede azalmış olup, bu grupta ortalama çinko düzeyi 0,696 mg/L, sağlıklı grupta ise 7,588 mg/L olarak belirlendi (P = 0,0001). Elde edilen sonuçlara bakıldığında atopik dermatitli köpeklerde gerek F-IAP gerekse Zn aktivitelerinde değişim meydana geldiğini öne sürmek yerinde olacaktır. Bulgular, sağaltım protokollerinde değişimi zorlayacaktır.

Kaynakça

  • Alpers, D. H., Mahmood, A., Engle, M., Yamagishi, F., & DeSchryver-Kecskemeti, K. (1994). The secretion of intestinal alkaline phosphatase (IAP) from the enterocyte. Journal of gastroenterology, 29, 63-67.Alpers, D. H.,Zhang, Y., & Ahnen, D. J. (1995). Synthesis and parallel secretion of rat intestinal alkaline phosphatase and a surfactant-like particle protein. American Journal of Physiology-Endocrinology and Metabolism, 268(6), E1205-E1214. https://doi.org/10.1152/ajpendo.1995.268.6.E1205
  • Avetisyan, M., Schill, E. M., & Heuckeroth, R. O. Building a second brain in the bowel. The Journal of clinical investigation, 2015;125(3), 899-907. https://doi.org/10.1172/JCI76307.
  • Cho, Y. E., Lomeda, R. A. R., Ryu, S. H., Sohn, H. Y., Shin, H. I., Beattie, J. H., & Kwun, I. S. (2007). Zinc deficiency negatively affects alkaline phosphatase and the concentration of Ca, Mg and P in rats. Nutrition research and practice, 1(2), 113-119. https://doi.org/10.4162/nrp.2007.1.2.113
  • Fawley, J., Koehler, S., Cabrera, S., Lam, V., Fredrich, K., Hessner, M., et al. & Gourlay, D. (2017). Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine. Journal of Surgical Research, 218, 35-42. https://doi.org/10.1016/j.jss.2017.03.049
  • Goldberg, R. F., Austen Jr, W. G., Zhang, X., Munene, G., Mostafa, G., Biswas, S., et al. & Hodin, R. A. (2008). Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proceedings of the National Academy of Sciences, 105(9), 3551-3556. https://doi.org/10.1073/pnas.0712140105
  • Goldstein, D. J., Rogers, C., & Harris, H. (1982). Evolution of alkaline phosphatases in primates. Proceedings of the National Academy of Sciences, 79(3), 879-883. https://doi.org/10.1073/pnas.79.3.879
  • Heath, M., Buckley, R., Gerber, Z., Davis, P., Linneman, L., Gong, Q., et al. & Kim, S. (2019). Association of intestinal alkaline phosphatase with necrotizing enterocolitis among premature infants. JAMA Network Open, 2(11), e1914996-e1914996.
  • Henthorn PS, Raducha M, Edwards YH, Weiss MJ, Slaughter C, et al. Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase. Proc Natl Acad Sci USA. 1987;84(5):1234-1238. doi: 10.1073/pnas.84.5.123 10. Huizinga, R., Kreft, K. L., Onderwater, S., Boonstra, J. G., Brands, R., Hintzen, R. Q., & Laman, J. D. (2012). Endotoxin-and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation. Journal of neuroinflammation, 9(1), 266. https://doi.org/10.1186/1742-2094-9-266
  • 1Koca, O., Dönmez, N. İkinci beyin: Bağırsak. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 2020, 15.2: 187-195. https://doi.org/10.17094/ataunivbd.701620
  • Lallès, J. P. (2015). Intestinal alkaline phosphatase in stool: a novel biomarker for metabolic diseases. EBioMedicine, 2(12), 1866. 10.1016/j.ebiom.2015.12.001
  • Lassenius, M. I., Fogarty, C. L., Blaut, M., Haimila, K., Riittinen, L., Paju, A., et al. & FinnDiane Study Group. (2017). Intestinal alkaline phosphatase at the crossroad of intestinal health and disease–a putative role in type 1 diabetes. Journal of internal medicine, 281(6), 586-600. https://doi.org/10.1111/joim.12607.
  • Luecke, R. W., Olman, M. E., & Baltzer, B. V. (1968). Zinc deficiency in the rat: effect on serum and intestinal alkaline phosphatase activities. The Journal of Nutrition, 94(3), 344-350. https://doi.org/10.1093/jn/94.3.344
  • Malo, M. S., Moaven, O., Muhammad, N., Biswas, B., Alam, S. N., Economopoulos, K. P., ... & Hodin, R. A. (2014). Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. American Journal of Physiology-Gastrointestinal and Liver Physiology, 306(10), G826-G838. https://doi.org/10.1152/ajpgi.00357.2013
  • Molnár, K., Vannay, Á., Szebeni, B., Bánki, N. F., Sziksz, E., Cseh, Á., ... & Veres, G. (2012). Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease. World journal of gastroenterology: WJG, 18(25), 3254. 10.3748/wjg.v18.i25.3254
  • Narisawa, S., Huang, L., Iwasaki, A., Hasegawa, H., Alpers, D. H., & Millán, J. L. (2003). Accelerated fat absorption in intestinal alkaline phosphatase knockout mice. Molecular and cellular biology, 23(21), 7525-7530. https://doi.org/10.1128/MCB.23.21.7525-7530.2003
  • Ramasamy, S., Nguyen, D. D., Eston, M. A., Nasrin Alam, S., Moss, A. K., Ebrahimi, F., ... & Hodin, R. A. (2011). Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis. Inflammatory bowel diseases, 17(2), 532-542. https://doi.org/10.1002/ibd.21377
  • Ray CS, Singh B, Jena I, Behera S, Ray S. Low alkaline phosphatase (ALP) in adult population an indicator of zinc (Zn) and magnesium (Mg) deficiency. Curr Res Nutr Food Sci. 2017;5(3). doi:10.12944/CRNFSJ.5.3.20
  • Tuin, A., Poelstra, K., de Jager-Krikken, A., Bok, L., Raaben, W., Velders, M. P., & Dijkstra, G. (2009). Role of alkaline phosphatase in colitis in man and rats. Gut, 58(3), 379-387. https://doi.org/10.1136/gut.2007.128868
  • Ural, K. (2024). ‘Bağırsak-Beyin-Deri Ekseni’: Retrospektif Olgu Tahlilleri (2009-2024) ve Tecrübeleri. Türkiye Sağlık Araştırmaları Dergisi, 5(3), 11-23.
  • Ural, K., Erdoğan, H., Erdoğan, S., Camkerten, İ., & Şahin, N.Circulating Serum Zonulin Levels Before and After Probiotic Enema Treatment in Dogs with Atopic Dermatitis: Randomized Clinical Study. Türkiye Klinikleri Journal of Veterinary Sciences, 2021; 12(2), 70-78. 10.5336/vetsci.2021-85829
  • Vallon, V., Muhlbauer, B., & Osswald, H. (2006). Adenosine and kidney function. Physiological reviews, 86(3), 901-940. https://doi.org/10.1152/physrev.00031.2005
  • von Frijtag Drabbe Künzel, J. K., van der Zee, J., & Ijzerman, A. P. Radical scavenging properties of adenosine and derivatives in vitro. Drug development research, 1996; 37(1), 48-54. https://doi.org/10.1002/(SICI)1098-2299(199601)37:1<48::AID-DDR3>3.0.CO;2-M
  • Xavier, R. J., & Podolsky, D. K. (2007). Unravelling the pathogenesis of inflammatory bowel disease. Nature, 448(7152), 427-434. https://doi.org/10.1038/nature06005
  • Zaher, D. M., El‐Gamal, M. I., Omar, H. A., Aljareh, S. N., Al‐Shamma, S. A., Ali, A. J., ... & Iqbal, J. (2020). Recent advances with alkaline phosphatase isoenzymes and their inhibitors. Archiv der Pharmazie, 353(5), e2000011. https://doi.org/10.1002/ardp.202000011.

The Gut Speaks Loudly: Measurement of Fecal Intestinal Alkaline Phosphatase Activity and Zinc Levels Along the Gut–Brain–Skin Axis in Dogs with Atopic Dermatitis

Yıl 2025, Cilt: 7 Sayı: 2, 43 - 47, 29.12.2025
https://doi.org/10.51755/turkvetj.1780858

Öz

This double-blind, randomized, prospective study was conducted based on the hypothesis of whether a biomarker belonging isoenzyme group as fecal intestinal alkaline phosphatase, which plays a critical role in gastrointestinal physiology and diseases, is diagnostically effective within the brain-gut-skin axis. In this study, focusing on the gut-brain-skin axis, the previous findings, experiences, and studies of the same research team were advanced one step further. The aims were: i) to determine whether the change in F-IAP activity in dogs with atopic dermatitis has the potential to serve as a novel gastroentero-dermatological health biomarker, ii) to evaluate its relationship with zinc levels, and iii) to assess whether its intestinal mucosa-protective effect is reduced in relation to the activity of this disease. In this study, F-IAP and serum zinc levels were measured in n=14 dogs with atopic dermatitis and n=12 healthy control dogs. The mean F-IAP level in dogs with atopic dermatitis was 13.8 IU/L, while it was 56.8 IU/L in the healthy control group (P = 0.0001). Similarly, serum zinc levels were significantly decreased in individuals with atopic dermatitis; the mean zinc level in this group was 0.696 mg/L, compared to 7.588 mg/L in the healthy group (P = 0.0001). Based on the findings, it would be appropriate to suggest that both F-IAP and Zn activities are altered in dogs with atopic dermatitis. These results may compel modifications in therapeutic protocols.

Kaynakça

  • Alpers, D. H., Mahmood, A., Engle, M., Yamagishi, F., & DeSchryver-Kecskemeti, K. (1994). The secretion of intestinal alkaline phosphatase (IAP) from the enterocyte. Journal of gastroenterology, 29, 63-67.Alpers, D. H.,Zhang, Y., & Ahnen, D. J. (1995). Synthesis and parallel secretion of rat intestinal alkaline phosphatase and a surfactant-like particle protein. American Journal of Physiology-Endocrinology and Metabolism, 268(6), E1205-E1214. https://doi.org/10.1152/ajpendo.1995.268.6.E1205
  • Avetisyan, M., Schill, E. M., & Heuckeroth, R. O. Building a second brain in the bowel. The Journal of clinical investigation, 2015;125(3), 899-907. https://doi.org/10.1172/JCI76307.
  • Cho, Y. E., Lomeda, R. A. R., Ryu, S. H., Sohn, H. Y., Shin, H. I., Beattie, J. H., & Kwun, I. S. (2007). Zinc deficiency negatively affects alkaline phosphatase and the concentration of Ca, Mg and P in rats. Nutrition research and practice, 1(2), 113-119. https://doi.org/10.4162/nrp.2007.1.2.113
  • Fawley, J., Koehler, S., Cabrera, S., Lam, V., Fredrich, K., Hessner, M., et al. & Gourlay, D. (2017). Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine. Journal of Surgical Research, 218, 35-42. https://doi.org/10.1016/j.jss.2017.03.049
  • Goldberg, R. F., Austen Jr, W. G., Zhang, X., Munene, G., Mostafa, G., Biswas, S., et al. & Hodin, R. A. (2008). Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proceedings of the National Academy of Sciences, 105(9), 3551-3556. https://doi.org/10.1073/pnas.0712140105
  • Goldstein, D. J., Rogers, C., & Harris, H. (1982). Evolution of alkaline phosphatases in primates. Proceedings of the National Academy of Sciences, 79(3), 879-883. https://doi.org/10.1073/pnas.79.3.879
  • Heath, M., Buckley, R., Gerber, Z., Davis, P., Linneman, L., Gong, Q., et al. & Kim, S. (2019). Association of intestinal alkaline phosphatase with necrotizing enterocolitis among premature infants. JAMA Network Open, 2(11), e1914996-e1914996.
  • Henthorn PS, Raducha M, Edwards YH, Weiss MJ, Slaughter C, et al. Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase. Proc Natl Acad Sci USA. 1987;84(5):1234-1238. doi: 10.1073/pnas.84.5.123 10. Huizinga, R., Kreft, K. L., Onderwater, S., Boonstra, J. G., Brands, R., Hintzen, R. Q., & Laman, J. D. (2012). Endotoxin-and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation. Journal of neuroinflammation, 9(1), 266. https://doi.org/10.1186/1742-2094-9-266
  • 1Koca, O., Dönmez, N. İkinci beyin: Bağırsak. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 2020, 15.2: 187-195. https://doi.org/10.17094/ataunivbd.701620
  • Lallès, J. P. (2015). Intestinal alkaline phosphatase in stool: a novel biomarker for metabolic diseases. EBioMedicine, 2(12), 1866. 10.1016/j.ebiom.2015.12.001
  • Lassenius, M. I., Fogarty, C. L., Blaut, M., Haimila, K., Riittinen, L., Paju, A., et al. & FinnDiane Study Group. (2017). Intestinal alkaline phosphatase at the crossroad of intestinal health and disease–a putative role in type 1 diabetes. Journal of internal medicine, 281(6), 586-600. https://doi.org/10.1111/joim.12607.
  • Luecke, R. W., Olman, M. E., & Baltzer, B. V. (1968). Zinc deficiency in the rat: effect on serum and intestinal alkaline phosphatase activities. The Journal of Nutrition, 94(3), 344-350. https://doi.org/10.1093/jn/94.3.344
  • Malo, M. S., Moaven, O., Muhammad, N., Biswas, B., Alam, S. N., Economopoulos, K. P., ... & Hodin, R. A. (2014). Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. American Journal of Physiology-Gastrointestinal and Liver Physiology, 306(10), G826-G838. https://doi.org/10.1152/ajpgi.00357.2013
  • Molnár, K., Vannay, Á., Szebeni, B., Bánki, N. F., Sziksz, E., Cseh, Á., ... & Veres, G. (2012). Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease. World journal of gastroenterology: WJG, 18(25), 3254. 10.3748/wjg.v18.i25.3254
  • Narisawa, S., Huang, L., Iwasaki, A., Hasegawa, H., Alpers, D. H., & Millán, J. L. (2003). Accelerated fat absorption in intestinal alkaline phosphatase knockout mice. Molecular and cellular biology, 23(21), 7525-7530. https://doi.org/10.1128/MCB.23.21.7525-7530.2003
  • Ramasamy, S., Nguyen, D. D., Eston, M. A., Nasrin Alam, S., Moss, A. K., Ebrahimi, F., ... & Hodin, R. A. (2011). Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis. Inflammatory bowel diseases, 17(2), 532-542. https://doi.org/10.1002/ibd.21377
  • Ray CS, Singh B, Jena I, Behera S, Ray S. Low alkaline phosphatase (ALP) in adult population an indicator of zinc (Zn) and magnesium (Mg) deficiency. Curr Res Nutr Food Sci. 2017;5(3). doi:10.12944/CRNFSJ.5.3.20
  • Tuin, A., Poelstra, K., de Jager-Krikken, A., Bok, L., Raaben, W., Velders, M. P., & Dijkstra, G. (2009). Role of alkaline phosphatase in colitis in man and rats. Gut, 58(3), 379-387. https://doi.org/10.1136/gut.2007.128868
  • Ural, K. (2024). ‘Bağırsak-Beyin-Deri Ekseni’: Retrospektif Olgu Tahlilleri (2009-2024) ve Tecrübeleri. Türkiye Sağlık Araştırmaları Dergisi, 5(3), 11-23.
  • Ural, K., Erdoğan, H., Erdoğan, S., Camkerten, İ., & Şahin, N.Circulating Serum Zonulin Levels Before and After Probiotic Enema Treatment in Dogs with Atopic Dermatitis: Randomized Clinical Study. Türkiye Klinikleri Journal of Veterinary Sciences, 2021; 12(2), 70-78. 10.5336/vetsci.2021-85829
  • Vallon, V., Muhlbauer, B., & Osswald, H. (2006). Adenosine and kidney function. Physiological reviews, 86(3), 901-940. https://doi.org/10.1152/physrev.00031.2005
  • von Frijtag Drabbe Künzel, J. K., van der Zee, J., & Ijzerman, A. P. Radical scavenging properties of adenosine and derivatives in vitro. Drug development research, 1996; 37(1), 48-54. https://doi.org/10.1002/(SICI)1098-2299(199601)37:1<48::AID-DDR3>3.0.CO;2-M
  • Xavier, R. J., & Podolsky, D. K. (2007). Unravelling the pathogenesis of inflammatory bowel disease. Nature, 448(7152), 427-434. https://doi.org/10.1038/nature06005
  • Zaher, D. M., El‐Gamal, M. I., Omar, H. A., Aljareh, S. N., Al‐Shamma, S. A., Ali, A. J., ... & Iqbal, J. (2020). Recent advances with alkaline phosphatase isoenzymes and their inhibitors. Archiv der Pharmazie, 353(5), e2000011. https://doi.org/10.1002/ardp.202000011.
Toplam 24 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Bilimleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Kerem Ural 0000-0003-1867-7143

Serdar Paşa 0000-0003-4957-9263

Hasan Erdoğan 0000-0001-5141-5108

Songül Erdoğan 0000-0002-7833-5519

Tahir Özalp 0000-0002-9873-0364

Gönderilme Tarihi 9 Eylül 2025
Kabul Tarihi 15 Ekim 2025
Yayımlanma Tarihi 29 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 7 Sayı: 2

Kaynak Göster

APA Ural, K., Paşa, S., Erdoğan, H., … Erdoğan, S. (2025). Bağırsakta bağırır: Atopik dermatitli köpeklerde ‘bağırsak-beyin-deri ekseninde’ fekal intestinal alkalen fosfataz aktivitesinin ve çinko seviyelerinin ölçümü. Turkish Veterinary Journal, 7(2), 43-47. https://doi.org/10.51755/turkvetj.1780858