Ürolitin-A’nın Non-Enfeksiyöz İshalli Buzağılarda Dışkı Skorları Üzerine Etkinliğinin Araştırılması

Abstract

Amaç: Bu araştırmada amaç, fonksiyonel gıda özelliğine sahip olan Ürolithin-a' (Ür-a)’nın enfeksiyöz olmayan ishalli buzağılarda doğal tedavi katılımcısı olarak etki edip edemeyeceğini multidisipliner olarak tespit etmektir. Gereç ve Yöntem: Bu amaçla 1 ila 28 günlük ishalli neonatal buzağılar arasından seçilerek, non-enfeksiyöz etiyolojiye sahip olan 40 buzağı çalışmaya dahil edildi. Enfeksiyöz ve enfeksiyöz olmayan ishaller arasında ayırıcı tanı için mikrobiyolojik, parazitolojik ve virolojik laboratuvar testlerine dayalı bir algoritma kullanıldı. Dışkı puanlaması 0 (normal kıvam) ile 3 (sıvı form) arasında bir ölçekle yapıldı. Ür-a, herhangi bir yan etki olmaksızın 10 ardışık gün boyunca 50 mg/kg dozunda oral yoldan uygulandı. Bulgular: Ür-a uygulamasına ilişkin olarak dışkı skorları (ortalama±standart sapma) önceki başlangıç değerleri olan 1.826 ± 0.242'ye (p < 0,01) kıyasla 0'a düştü. Sonuç: Elde edilen veriler, bu ön sonuçların non-infeksiyöz ishalli buzağılarda Ür-a'nın gastrointestinal sağlığı destekleyici etkinliğine sahip olabileceğini gösterebilir. İleriki çalışmaların gerçekleştirilmesi gerekliliği, bir sonraki çalışmamızın amacı olacaktır

Keywords

• Buzağı
• ishal
• non-enfeksiyöz
• urolithin-a

Investigation Of The Effectiveness Of Urolithin-A On Fecal Scores In Calves With Non-İnfectious Diarrhea

Abstract

Aim: The aim of this study was to determine multidisciplinary whether Urolithin-a (Ur-a), which has functional food properties, can be effective as a natural treatment agent in calves with non-infectious diarrhea. Materials and Methods: For this purpose, neonatal calves with diarrhea aged 1 to 28 days and 40 calves selected with non-infectious etiology were included in the study. An algorithm based on microbiological, parasitological and virological laboratory tests was used for differential diagnosis between infectious and non-infectious diarrhea. Stool scoring was done on a scale from 0 (normal consistency) to 3 (liquid form). Ur-a was administered orally at a dose of 50 mg/kg for 10 consecutive days without any side effects. Results: With regard to Ur-a administration, fecal scores (mean±standard deviation) decreased to 0 compared to the previous baseline values of 1.826 ± 0.242 (p < 0.01). Conclusion: The obtained data may indicate that these preliminary results may have the efficacy of Ur-a in supporting gastrointestinal health in calves with non-infectious diarrhea. The need for further studies will be the aim of our next study.

Keywords

• Calf
• diarrhea
• non-infectious
• Urolithin-a

References

1. United Nations, Department of Economic and Social Affairs, Population Division. World Population Prospects Highlights (ST/ESA/SER.A/423). Population.un.org Web site Feb 17, 2019.. Available at: https://population.un.org/wpp/publications/files/wpp2019_highlights.pdf
2. Myers A, Lithgow GJ. Drugs that target aging: How do we discover them? Expert Opin Drug Discov. 2019;14(6):541-548.
3. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11(4):675-682.
4. Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246-1256.
5. Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.
6. Cerdá B, Espín JC, Parra S, Martínez P, Tomás-Barberán FA. The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. Eur J Nutr. 2004;43(4):205-2220.
7. Cerdá B, Tomás-Barberán FA, Espín JC. Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability. J Agric Food Chem. 2005;53(2):227-235.
8. González-Sarrías A, Larrosa M, Tomás-Barberán FA, Dolara P, Espín JC. NF-κB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts. Br J Nutr. 2010;104(4):503-512.

9. Cortés-Martín A, Selma MV, Tomás-Barberán FA, González-Sarrías A, Espín JC. Where to look into the puzzle of polyphenols and health? The postbiotics and gut microbiota associated with human metabotypes. Mol Nutr Food Res. 2020;64(9):e1900952.
10. Gaya P, Peirotén Á, Medina M, Álvarez I, Landete JM. Bifidobacterium pseudocatenulatum INIA P815: The first bacterium able to produce urolithins A and B from ellagic acid. J Funct Foods. 2018;45:95-99.
11. Zhang X, Fang Y, Yang G, Hou X, Hai Y, Xia M, et al. Isolation and characterization of a novel human intestinal Enterococcus faecium FUA027 capable of producing urolithin A from ellagic acid. Front Nutr. 2022;9:1039697.
12. Beltrán D, Romo-Vaquero M, Espín JC, Tomás-Barberán FA, Selma MV. Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family Eggerthellaceae, isolated from human gut. Int J Syst Evol Microbiol. 2018;68(5):1707-1712.
13. Selma MV, Beltrán D, Luna MC, Romo-Vaquero M, García-Villalba R, Mira A, et al. Isolation of human ıntestinal bacteria capable of producing the bioactive metabolite ısourolithin a from ellagic acid. Front Microbiol. 2017;8:1521.
14. Watanabe H, Kishino S, Kudoh M, Yamamoto H, Ogawa J. Evaluation of electron-transferring cofactor mediating enzyme systems involved in urolithin dehydroxylation in Gordonibacter urolithinfaciens DSM 27213. J Biosci Bioeng. 2020;129(5):552-557.
15. Singh A, D’Amico D, Andreux PA, Dunngalvin G, Kern T, Blanco-Bose W, et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2022;76(2):297-308.
16. D’Amico D, Andreux PA, Valdés P, Singh A, Rinsch C, Auwerx J. Impact of the natural compound urolithin a on health, disease, and aging. Trends Mol Med. 2021;27(7):687-699.
17. Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-dit-Félix AA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med. 2016;22(8):879-888.
18. Ballesteros-Álvarez J, Nguyen W, Sivapatham R, Rane A, Andersen JK. Urolithin A reduces amyloid-beta load and improves cognitive deficits uncorrelated with plaque burden in a mouse model of Alzheimer’s disease. Geroscience. 2023;45(2):1095-1113.
19. McGuirk SM. Disease management of dairy calves and heifers. Vet Clin North Am Food Anim Pract. 2008;24(1):139-153.
20. Vaatstra B. Calf diarrhoea. VetScript. 2018;52-55.
21. Andreux PA, Blanco-Bose W, Ryu D, Burdet F, Ibberson M, Aebischer P, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1(6):595-603.
22. Singh A, D’Amico D, Andreux PA, Fouassier AM, Blanco-Bose W, Evans M, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633.
23. Liu S, D’Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, et al. Effect of Urolithin A supplementation on muscle endurance and mitochondrial health in older adults: A randomized clinical trial. JAMA Netw Open. 2022;5(1):e2144279.
24. Huang JR, Zhang MH, Chen YJ, Sun YL, Gao ZM, Li ZJ, et al. Urolithin A ameliorates obesity-induced metabolic cardiomyopathy in mice via mitophagy activation. Acta Pharmacol Sin. 2023;44(2):321–331.
25. Albasher G, Alkahtani S, Al-Harbi LN. Urolithin A prevents streptozotocin-induced diabetic cardiomyopathy in rats by activating SIRT1. Saudi J Biol Sci. 2022;29(2):1210–1220.
26. Gasperotti M, Passamonti S, Tramer F, Masuero D, Guella G, Mattivi F, et al. Fate of microbial metabolites of dietary polyphenols in rats: Is the brain their target destination? ACS Chem Neurosci. 2015;6(8):1341–1352.
27. Yasuda T, Takagi T, Asaeda K, Hashimoto H, Kajiwara M, Azuma Y, et al. Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis. Sci Rep. 2024;14:15706.
28. Avila-Gálvez M, García-Villalba R, Martínez-Díaz F, Ocaña-Castillo B, Monedero-Saiz T, Torrecillas-Sánchez A, et al. Metabolic profiling of dietary polyphenols and methylxanthines in normal and malignant mammary tissues from breast cancer patients. Mol Nutr Food Res. 2019;63(9):e1801239.
29. Kubota D, Sato M, Udono M, Kohara A, Kudoh M, Ukawa Y, et al. Activation of the gut–brain interaction by Urolithin A and its molecular basis. Nutrients. 2024;16(19):3369.
30. Zhao R, Long X, Yang J, Du L, Zhang X, Li J, et al. Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet. Food Funct. 2019;10(12):8273–8285.
31. Toney AM, Fox D, Chaidez V, Ramer-Tait AE, Chung S. Immunomodulatory role of Urolithin A on metabolic diseases. Biomedicines. 2021;9:192.
32. Salminen JP, Roslin T, Karonen M, Sinkkonen J, Pihlaja K, Pulkkinen P. Seasonal variation in the content of hydrolyzable tannins, flavonoid glycosides, and proanthocyanidins in oak leaves. J Chem Ecol. 2004;30:1693–1711.
33. Makkar HPS, Singh B, Dawra RK. Effect of tannin-rich leaves of oak on various microbial activities of the rumen. Br J Nutr. 1988;60:287–296.
34. Shabtay A, Eitam H, Tadmor Y, Orlov A, Meir A, Weinberg P, et al. Nutritive and antioxidative potential of fresh and stored pomegranate industrial byproduct as a novel beef cattle feed. J Agric Food Chem. 2008;56:10063–10070.
35. Murdiati TB, McSweeney CS, Lowry JB. Metabolism in sheep of gallic acid, tannic acid and hydrolysable tannin from Terminalia oblongata. Aust J Agric Resour. 1992;43:1307–1319.
36. Zhu J, Filippich LJ. Rumen involvement in sheep tannic acid metabolism. Vet Hum Toxicol. 1995;37:436–440.
37. Doce RR, Hervas G, Belenguer A, Toral PG, Giráldez FJ, Frutos P. Effect of the administration of young oak (Quercus pyrenaica) leaves to cattle on ruminal fermentation. Anim Feed Sci Technol. 2009;150:75–85.
38. Garg SK, Makkar HPS, Nagal KB, Sharma SK, Wadhwa DR, Singh B. Toxicological investigations into oak (Quercus incana) leaf poisoning in cattle. Vet Hum Toxicol. 1992;34:161–164.
39. González-Barrio R, Truchado P, Villalba R, Hervás G, Frutos P, Espín JC, et al. Metabolism of oak leaf ellagitannins and Urolithin production in beef cattle. J Agric Food Chem. 2012;60:3068–3077.
40. Mena P, Dall’Asta M, Calani L, Brighenti F, Del Rio D. Gastrointestinal stability of Urolithins: An in vitro approach. Eur J Nutr. 2017;56(1):99–106.