Evaluation of Some Intestinal Biomarkers in the Determination of Intestinal Damage in Calves with Coccidiosis

M. K. Durgut, M. Ok


This study aimed to assess the usefulness of injury biomarkers specific to the intestines in identifying the presence and degree of intestinal epithelial damage in coccidiosis-infected calves. Forty calves of various breeds and sexes, aged 21 days to 60 days, were used in the study. Of these, 30 were in the experimental group, and 10 were healthy control. The McMaster Oocyte counting technique was used to diagnose Eimeria and confirm clinical coccidiosis. Cases with clinical signs and more than 5,000 oocysts in gram feces were included in the study. All calves had blood samples drawn at the 0th hours and 72nd hours. Blood gas measurements were performed with a blood gas analyzer. Hemogram was performed with an automated hematologic analyzer. Bovine-specific enzyme-linked immunosorbent analysis (ELISA) test kits were used to measure the intestinal fatty acid binding protein (I-FABP), trefoil factor-3 (TFF-3), intestinal alkaline phosphatase (IAP), claudin-3 (CLD-3), intestinal smooth muscle actin (ACTG2), and interleukin-8 (IL-8) biomarkers from serum samples. Calves with coccidiosis received a single dose of toltrazuril (15 mg/kg) and supportive care. Before treatment (0th hours) in coccidiosis-infected calves, serum I-FABP and CLD-3 levels were greater than in healthy calves (p<0.05), and after treatment (72nd hours), serum TFF-3 and ACTG2 levels were higher than in healthy calves. There was a significant decrease in serum IL-8 levels in coccidiosis-infected calves after treatment (72nd hours) compared to pre-treatment (0th hours) (p<0.05). I-FABP, TFF-3, CLD-3, ACTG2, and IL-8 are helpful and reliable biomarkers that can be utilized to assess the presence of intestinal epithelium injury in coccidiosis-infected calves.


Adriaanse, M. P., A. Mubarak, R. G. Riedl, F. J. W. T. Kate, J. G. M. C. Damoiseaux, W. A. Buurman, R. H. J. Houwen, & A. C. E. Vreugdenhil. 2017. Progress towards non-invasive diagnosis and follow-up of celiac disease in children; A prospective multicentre study to the usefulness of plasma I-FABP. Sci. Rep. 7:1-10.
Ahmed, Y. N., G. A. Al-Shamma, & A. S. Hassen. 2021. Evaluation of serum level of claudin‐3 and its association with disease severity in patients with psoriasis in Iraqi patients. Journal University Shanghai Science Technology 23:1031-9. https://doi.org/10.51201/JUSST/21/09648
Ay, C. D., G. E. Tuna, G. S. E. Asici, B. Ulutas, & H. Voyvoda. 2022. Serum intestinal fatty acid-binding protein and calprotectin concentrations to assess clinical severity and prognosis of canine parvovirus enteritis. Kafkas Universitesi Veteriner Fakultesi Dergisi 28:105-114.
Bangoura, B. & K. D. Bardsley. 2020. Ruminant coccidiosis. Veterinary Clinics North America: Food Animal Practice. 36:187-203. https://doi.org/10.1016/j.cvfa.2019.12.006
Bangoura, B., M. C. Mundt, R. Schmäschke, B. Westphal, & A. Daugschies. 2012. Prevalence of Eimeria bovis and Eimeria zuernii in German cattle herds and factors influencing oocyst excretion. Parasitol. Res. 110:875–881. https://doi.org/10.1007/s00436-011-2569-z
Benkoe, T. M., T. P. Mechtler, M. Weninger, M. Pones, W. Rebhandl, & D. C. Kasper. 2014. Serum levels of interleukin-8 and gut-associated biomarkers in diagnosing necrotizing enterocolitis in preterm infants. J. Pediatr. Surg. 49:1446-1451. https://doi.org/10.1016/j.jpedsurg.2014.03.012
Bilski, J., A. Mazur-Bialy, D. Wojcik, J. Zahradnik-Bilska, B. Brzozowski, M. Magierowski, T. Mach, K. Magierowska, & T. Brzozowski. 2017. The role of intestinal alkaline phosphatase in inflammatory disorders of gastrointestinal tract. Mediators Inflamm. 2017:9074601. https://doi.org/10.1155/2017/9074601
Cascais- Figueiredo, T., P. A. Teixeira, M. Fantinatti, M. L. S. Freitas, J. R. S. Oliveira, C. H. Coelho, S. M. Singer, & A. M. D. Cruz. 2020. Giardiasis alters intestinal fatty acid binding protein (I-FABP) and plasma cytokines levels in children in Brazil. Pathogens 9:7. https://doi.org/10.3390/pathogens9010007
Coufal, S., A. Kokesova, H. Tlaskalova-Hogenova, B. Frybova, J. Snajdauf, M. Rygl, & M. Kverka. 2020. Urinary I-FABP, L-FABP, TFF-3, and SAA can diagnose and predict the disease course in necrotizing enterocolitis at the early stage of disease. J. Immunol. Res. 2020:3074313. https://doi.org/10.1155/2020/3074313
Daig, R., T. Andus, E. Aschenbrenner, W. Falk, J. Schölmerich, & V. Gross. 1996. Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut 38:216-222. https://doi.org/10.1136/gut.38.2.216
Eckmann, L., H. C. Jung, C. Schürer-Maly, A. Panja, E. Morzycka-Wroblewska, & M. F. Kagnoff. 1993. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8. Gastroenterology 105:1689-97. https://doi.org/10.1016/0016-5085(93)91064-O
Eglenti, N., S. Kozat, & V. Denizhan. 2020. Investigation of immunoglobulin (IgE, IgA, IgG, IgM) concentrations in calves naturally infected with coccidiosis. Journal Istanbul Veterinary Sciences 4:1-7. https://doi.org/10.30704/http-www-jivs-net.691671
Espinoza, I., S. Agarwal, A. Reddy, V. Shenoy, C. Subramony, M. Sakiyama, L. Fair, T. Poosarla, X. Zhou, W. S. Orr, & C. Lahr. 2021. Expression of trefoil factor 3 is decreased in colorectal cancer. Oncol. Rep. 45:254-264. https://doi.org/10.3892/or.2020.7829
Evennett, N., E. Cerigioni, N. J. Hall, A. Pierro, & S. Eaton. 2014. Smooth muscle actin as a novel serologic marker of severe intestinal damage in rat intestinal ischemia–reperfusion and human necrotising enterocolitis. J. Surg. Res. 191:323-330. https://doi.org/10.1016/j.jss.2014.04.020
Fawley, J. & D. M. Gourlay. 2016. Intestinal alkaline phosphatase: A summary of its role in clinical disease. J. Surg. Res. 202:225-234. https://doi.org/10.1016/j.jss.2015.12.008
Gulersoy, E., M. Ok, R. Yildiz, E. Koral, M. Ider, M. Sevinc, & A. Zhunushova. 2020. Assessment of intestinal and cardiac-related biomarkers in dogs with parvoviral enteritis. Pol. J. Vet. Sci. 23:211-219.
Guzel, M., E. M. Sözüer, Ö. Salt, İ. İkizceli, & O. Akdur. 2014. The value of the serum I-FABP level for diagnosing acute mesenteric ischemia. Surg. Today 44:2072-2076. https://doi.org/10.1007/s00595-013-0810-3
Howarth, C., J. Banerjee, S. Eaton, & N. Aladangady. 2022. Biomarkers of gut injury in neonates–where are we in predicting necrotising enterocolitis?. Front. Pediatr. 10:1048322. https://doi.org/10.3389/fped.2022.1048322
Huo, R., H. Liu, J. Chen, H. Sheng, & L. Miao. 2021. Serum HMGB1 level is correlated with serum I-FABP level in neonatal patients with necrotizing enterocolitis. BMC Pediatr. 21:355. https://doi.org/10.1186/s12887-021-02818-6
Kampanatkosol, R., T. Thomson, O. Habeeb, L. Glynn, P. J. DeChristopher, S. Yong, W. Jeske, A. Maheshwari, & J. Muraskas. 2014. The relationship between reticulated platelets, intestinal alkaline phosphatase, and necrotizing enterocolitis. J. Pediatr. Surg. 49:273-276. https://doi.org/10.1016/j.jpedsurg.2013.11.037
Khadaroo, R. G., S. Fortis, S. Y. Salim, C. Streutker, T. A. Churchill, & H. Zhang. 2014. I-FABP as biomarker for the early diagnosis of acute mesenteric ischemia and resultant lung injury. PLoS ONE 9:e115242. https://doi.org/10.1371/journal.pone.0115242
Koval, M. 2013. Claudin heterogeneity and control of lung tight junctions. Annu. Rev. Physiol. 75:551-567. https://doi.org/10.1146/annurev-physiol-030212-183809
Kühn, F., F. Adiliaghdam, P. M. Cavallaro, S. R. Hamarneh, A. Tsurumi, R. S. Hoda, A. R. Munoz, Y. Dhole, J. M. Ramirez, E. Liu, R. Vasan, Y. Liu, E. Samarbafzadeh, R. A. Nunez, M. Z. Farber, V. Chopra, M. S. Malo, L. G. Rahme, & R. A. Hodin. 2020. Intestinal alkaline phosphatase targets the gut barrier to prevent aging. JCI Insight 5:e134049. https://doi.org/10.1172/jci.insight.134049
Lattanzi, G., V. Cenni, S. Marmiroli, C. Capanni, E. Mattioli, L. Merlini, S. Squarzoni, & N. M. Maraldi. 2003. Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts. Biochem. Biophys. Res. Commun. 303:764-770. https://doi.org/10.1016/S0006-291X(03)00415-7
Lu, Z., L. Ding, Q. Lu, & Y. H. Chen. 2013. Claudins in intestines: Distribution and functional significance in health and diseases. Tissue Barriers 1:24978. https://doi.org/10.4161/tisb.24978
Malo, M. S., O. Moaven, N. Muhammad, B. Biswas, S. N. Alam, K. P. Economopoulos, S. S. Gul, S. R. Hamarneh, N. S. Malo, A. Teshager, & M. M. R. Mohamed. 2014. Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. Am. J. Physiol. Gastrointest. Liver Physiol. 306:826-838. https://doi.org/10.1152/ajpgi.00357.2013
Mennigen, R., K. Nolte, E. Rijcken, M. Utech, B. Loeffler, N. Senninger, & M. Bruewer. 2009. Probiotic mixture VSL# 3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am. J. Physiol. 296:1140-1149. https://doi.org/10.1152/ajpgi.90534.2008
Ng, E. W., T. C. Poon, H. S. Lam, H. M. Cheung, T. P. Ma, K. Y. Chan, R. P. Wong, K. T. Leung, M. M. Lam, K. Li, & P. C. Ng. 2013. Gut-associated biomarkers L-FABP, I-FABP, and TFF3 and LIT score for diagnosis of surgical necrotizing enterocolitis in preterm infants. Ann. Surg. 258:1111-1118. https://doi.org/10.1097/SLA.0b013e318288ea96
Nieto, J. E., B. M. Aldridge, P. M. Beldomenico, M. Aleman, & J. R. Snyder. 2005. Characterization of equine intestinal fatty acid binding protein and its use in managing horses with colic. Am. J. Vet. Res. 66:223-232. https://doi.org/10.2460/ajvr.2005.66.223
Nakov, R., T. Velikova, V. Nakov, G. Ianiro, V. Gerova, & L. Tankova. 2019. Serum trefoil factor 3 predicts disease activity in patients with ulcerative colitis. Eur. Rev. Med. Pharmacol. Sci. 23:788-794.
Ok, M., M. Ider, M. K. Durgut, O. Ceylan, & A. Ertürk. 2019. Evaluation of the efficacy of toltrazuril in the treatment of acute Coccidiosis of lamb and kid. Journal Dicle University Faculty Veterinary Medicine 12:37-40.
Ok, M., R. Yildiz, F. Hatipoglu, N. Baspinar, M. Ider, K. Üney, A. Ertürk, M. K. Durgut, & F. Terzi. 2020. Use of intestine-related biomarkers for detecting intestinal epithelial damage in neonatal calves with diarrhea. Am. J. Vet. Res. 81:139-146. https://doi.org/10.2460/ajvr.81.2.139
Oldenburger, I. B., V. M. Wolters, T. Kardol‐Hoefnagel, R. H. Houwen, & H. G. Otten. 2018. Serum intestinal fatty acid-binding protein in the non-invasive diagnosis of celiac disease. APIMS 126:186-190. https://doi.org/10.1111/apm.12800
Park, S. Y., J. Y. Kim, S. M. Lee, J. O. Chung, J. H. Seo, S. Kim, D. H. Kim, C. H. Park, J. K. Ju, Y. E. Joo, & J. H. Lee. 2018. Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn’s disease. BMC Gastroenterol. 18:1-6. https://doi.org/10.1186/s12876-018-0904-x
Pontell, L., P. Sharma, L. R. Rivera, M. Thacker, Y. H. Tan, J. A. Brock, & J. B. Furness. 2011. Damaging effects of ishcemia/reperfusion on intestinal muscle. Cell Tissue Res. 343:411-419. https://doi.org/10.1007/s00441-010-1096-z
Reinecke, R. K. 1983. Veterinary Helminthology. Butterworth & Co. (SA) (Pty.).
Santos, G. M., S. Ismael, J. Morais, J. R. Araújo, A. Faria, C. Calhau, & C. Marques. 2022. Intestinal alkaline phosphatase: A review of this enzyme role in the intestinal barrier function. Microorganisms 10:746. https://doi.org/10.3390/microorganisms10040746
Sarıkaya, M., B. Ergül, Z. Doğan, L. Filik, M. Can, & L. Arslan. 2015. Intestinal fatty acid binding protein (I-FABP) as a promising test for Crohn’s disease: A preliminary study. Clin. Lab. 61:87-91. https://doi.org/10.7754/Clin.Lab.2014.140518
Sen, I., V. Altunok, M. Ok, A. Coskun, & P. D. Constable. 2009. Efficacy of oral rehydration therapy solutions containing sodium bicarbonate or sodium acetate for treatment of calves with naturally acquired diarrhea, moderate dehydration, and strong ion acidosis. J. Am. Vet. Med. Assoc. 234:926-34. https://doi.org/10.2460/javma.234.7.926
Seo, Y. M., Y. K. Lin, S. A. Im, I. K. Sung, Y. A. Youn, S. S. Hospital, & C. M. College. 2021. Interleukin 8 may predict surgical necrotizing enterocolitis in infants born less than 1500 g. Cytokine 137:155343. https://doi.org/10.1016/j.cyto.2020.155343
Shaaban, A. I., O. A. Alfqy, H. M. Shaaban, Y. H. A-Maqsoud, & E. H. Assar. 2021. Potential role of serum intestinal fatty acid-binding protein as a marker for early prediction and diagnosis of necrotizing enterocolitis in preterm neonates. J. Indian Assoc. Pediatr. Surg. 26:393. https://doi.org/10.4103/jiaps.JIAPS_218_20
Sikora, M., M. Chrabąszcz, A. Waśkiel‐Burnat, A. Rakowska, M. Olszewska, & L. Rudnicka. 2019. Claudin‐3–a new intestinal integrity marker in patients with psoriasis: association with disease severity. J. Eur. Acad. Dermatol. Venereol. 33:1907-1912. https://doi.org/10.1111/jdv.15700
Srivastava, S., S. Kedia, S. Kumar, V. P. Mouli, R. Dhingra, V. Sachdev, V. Tiwari, L. Kurrey, R. Pradhan, & V. Ahuja. 2015. Serum human trefoil factor 3 is a biomarker for mucosal healing in ulcerative colitis patients with minimal disease activity. J. Crohn’s Colitis. 9:575-579. https://doi.org/10.1093/ecco-jcc/jjv075
Sudhakara, R. B., S. Sivajothi, & V. C. Rayulu. 2015. Clinical coccidiosis in adult cattle. J Parasit. Dis. 39:557-559. https://doi.org/10.1007/s12639-013-0395-1
Sultana, R., A. Maqbool, M. Z. Ahmad, Ch. Z. Iqbal, & Ch. S. Ilyas. 2017. Chemotherapy of Coccidiosis in calves. Arch. Vet. Sci. Technol. 6:1-4. https://doi.org/10.29011/2637-9988/100029
Taniguchi, Y., Y. Kurokawa, T. Takahashi, J. Mikami, Y. Miyazaki, K. Tanaka, T. Makino, M. Yamasaki, K. Nakajima, M. Mori, & Y. Doki. 2018. Prognostic value of trefoil factor 3 expression in patients with gastric cancer. World J. Surg. 42:3997-4004. https://doi.org/10.1007/s00268-018-4737-0
Yildiz, I. B. & M. Ok. 2022. Evaluation of selected intestinal damage biomarkers to determine intestinal damage in dogs with isosporosis. Magy. Allatorvosok Lapja.144:101-113.
Yildiz, R., M. Ok, M. Ider, U. Aydogdu, A. Naseri, K. Parlak, & E. Gulersoy. 2018. Evaluation of intestinal damage biomarkers in calves with atresia coli. J. Vet. Res. 62:379-384. https://doi.org/10.2478/jvetres-2018-0054
Yildiz, R., M. Ok, M. Ider, A. Akar, A. Naseri, & E. Koral. 2019. The changes in biomarkers for necrotising enterocolitis in premature calves with respiratory distress syndrome. Vet. Med. 64:440-447. https://doi.org/10.17221/37/2019-VETMED
Zeissig, S., N. Bürgel, D. Günzel, J. Richter, J. Mankertz, U. Wahnschaffe, & J. D. Schulzke. 2007. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 56:61-72. https://doi.org/10.1136/gut.2006.094375
Zenger, S., I. D. Piroğlu, A. Çevik, Y. Özcabi, D. Fakıoğlu, M. Senol, M. M. Altıntaş, N. Bildik, & T. Yücel, 2021. The importance of serum intestinal fatty acid-binding protein for the early diagnosis of acute mesenteric ischemia. Ulus. Travma Derg. 27:278-283. https://doi.org/10.14744/tjtes.2020.35823


M. K. Durgut
mkaan.durgut@selcuk.edu.tr (Primary Contact)
M. Ok
DurgutM. K., & OkM. (2023). Evaluation of Some Intestinal Biomarkers in the Determination of Intestinal Damage in Calves with Coccidiosis. Tropical Animal Science Journal, 46(2), 221-230. https://doi.org/10.5398/tasj.2023.46.2.221

Article Details

List of Cited By :

Crossref logo