Effects of dietary supplementation of bentonite and Saccharomyces cerevisiae cell wall on acute-phase protein and liver function in high-producing dairy cows during transition period

  • Seyed Amin Razavi
  • Mehrdad Pourjafar
  • Ali HajimohammadiEmail author
  • Reza Valizadeh
  • Abbas Ali Naserian
  • Richard Laven
  • Kristina Ruth Mueller
Regular Articles


The aim of this study was to investigate the efficacy of dietary endotoxin binders [bentonite (BEN) and Saccharomyces cerevisiae cell wall (SCW)] on acute-phase protein (APP) response and liver function in cows during the transition period. Twenty-four multiparous Holstein cows were randomly assigned to one of four treatment groups. The experimental groups consisted of (1) the basal diet (BD) + SCW, (2) BD + SCW + BEN, (3) BD + BEN, and (4) BD (control). Blood samples were taken at 1, 3 and 4 weeks before and 1 and 3 weeks after parturition and serum concentrations of non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), glucose, haptoglobin (Hp), serum amyloid A(SAA), albumin, g-glutamyl transferase (GGT), aspartate aminotransferase (AST), cholesterol, iron, and lipopolysaccharide (LPS) were measured. The concentrations of LPS, SAA, albumin, and Hp in the blood were within reference range at all times. The level of blood LPS was not high enough to initiate an APP response. Mean BHBA concentration was highest at 1 week after calving. For NEFA, the pattern was similar, with a peak at 1 week after calving. Cholesterol concentration was lower in the SCW group, probably due to a lower lipoprotein concentration. Mean AST concentration was highest at 1 week after calving, especially in the SCW + BEN group. The results of a current study showed that, if the carbohydrate level is not high in the diet to cause rumen acidosis, it is not profitable to supplement BEN and SCW for adsorbing endotoxins in the diet, in transition cows.

Key words

Endotoxin binders Dairy cow Acute-phase protein response Liver function Transition period 



This study was financed by Ph.D student project grant by School of Veterinary Medicine, Shiraz University, Shiraz, Iran. The authors would like to thank the Moghufat Malek industry for provision of cows especially Mr.Miri, Mr.Naghavi and Mr.Ershadi.

Compliance with ethical standards

Statement of Animal Rights

All animals were treated in accordance with the regulations on the guidelines of the Iranian Council of Animal Care (1995), and the experiment was approved by the Institutional Animal Care Committee for Animals Used in Research and We further followed the recommendations of European Council Directive (86/609/EC) of November 24, 1986, regarding the standards of protecting animals used for experimental purposes.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Alsemgeest, S.P., Taverne, M.A., Boosman, R., Van Der Weyden, B.C., Gruys, E., 1993. Peripartum acute-phase protein serum amyloid-A concentration in plasma of cows and fetuses. American Journal of Veterinary Research 54, 164–167.Google Scholar
  2. Alsemgeest, S.P.M., Kalsbeek, H.C., Wensing, T.H., Koeman J.P., Van Ederen, A.M., Gruys E., 1994.Concentrations of serum amyloid A (SAA) and haptoglobin (Hp) as parameters of inflammatory diseases in cattle. Veterinary Quarterly,16, 21–23.CrossRefGoogle Scholar
  3. Alsemgeest, S.P., Lambooy, I.E., Wierenga, H.K., Dieleman, S.J., Meerkerk, B., VanEderen, A.M., Niewold, T.A., 1995. Influence of physical stress on the plasma concentration of serum amyloid-A (SAA) and haptoglobin (Hp) in calves. Veterinary Quarterly 17, 9–12.CrossRefGoogle Scholar
  4. Ametaj, B.N., 2005. A new understanding of the causes of fatty liver in dairy cows. Advanced Dairy Science and Technology, 17, 97–112.Google Scholar
  5. Ametaj, B. N., Q. Zebeli, and S. Iqbal. 2010. Nutrition, microbiota, and endotoxin-related diseases in dairy cows. Revista Brasileira de Zootecnia, 39:433–444. CrossRefGoogle Scholar
  6. Andersen, P. H. 2003. Bovine endotoxicosis—some aspects of relevance to production diseases. A review. Acta Veterinaria Scandinavica, 98:141–155. DOI: Google Scholar
  7. Andersen, P. H., Jarlov, N., 1990. Investigation of the possible role of endotoxin, TXA2, PG12 and PGE2 in experimentally induced rumen acidosis in cattle. Acta Veterinaria Scandinavica. 31:27–38.Google Scholar
  8. Andersen, P. H., Bergelin, B., Christensen, K. A., 1994. Effect of feeding regimen on concentration of free endotoxin in ruminal fluid of cattle. Journal of Animal Science, 72:487–491.CrossRefGoogle Scholar
  9. Andersen, P.H., Jarløv N., Hesselholt, M., Bæk, L., 1996. Studies on in vivo endotoxin plasma disappearance times in cattle. Journal of Veterinary Medicine, A. 43, 93-101.CrossRefGoogle Scholar
  10. Baydar, E. & Dabak, M., 2014, Serum iron as an indicator of acute inflammation in cattle. Journal of Dairy Science, 97, 222-228. DOI: CrossRefGoogle Scholar
  11. Berczi, I., Bertók, L., Bereznai, T., 1966. Comparative studies on the toxicity of Escherichia coli lipopolysaccharide endotoxin in various animal species. Canadian Journal of Microbiology, 12, 1070–1071.CrossRefGoogle Scholar
  12. Bertoni, G., and E. Trevisi. 2013. Use of the liver activity index and other metabolic variables in the assessment of metabolic health in dairy herds. Veterinary Clinics of North America: Food Animal Practice, 29:413–431. DOI: Scholar
  13. Bobe, G., Young, J.W., Beitz, D.C., 2004. Invited review: pathology, etiology, prevention, and treatment of fatty liver in dairy cows. Journal of Dairy Science, 87, 3105–3124. DOI:
  14. Body, J.W., Douglas, T.A., Gould, C.M. and Grimes, F.C., 1964. The interpretation of serum enzyme assay in cattle. Veterinary Record, 76, 567-574.Google Scholar
  15. Bogin, E., Avidan, Y., Meron, M., Soback, S., Brenner, G., 1988. Biochemical changes associated with the fatty liver syndrome in cows. Journal of Comparative Pathology, 98, 337-347.CrossRefGoogle Scholar
  16. Bolognani, F., Rumney, C. J., Rowland, I. R., 1997. Influence of carcinogen binding by lactic acid-producing bacteria on tissue distribution and in vitro mutagenicity of dietary carcinogens. Food and Chemical Toxicology, 35, 535–545.CrossRefGoogle Scholar
  17. Bradford, B.J., Mamedova, L.K., Minton, J.E., Drouillard, J.S., Johnson, B.J., 2009. Daily injection of tumor necrosis factor-{alpha} increases hepatic triglycerides and alters transcript abundance of metabolic genes in lactating dairy cattle. Journal of Nutrition, 139, 1454–1456. DOI: Scholar
  18. Brady, D., Stoll, A. D., Strake, L., Dunkan, J. R., 1994. Chemical and enzymatic extraction of heavy metal binding polymera from isolated cell walls of Saccharomyces cerevisiae. Biotechnology and Bioengineering, 44, 297–302.CrossRefGoogle Scholar
  19. Breierova, E., Vajczikova, I., Sasinkova, V., Stratilova, E., Fiserac, M., Gregor, T., et al., 2002. Biosorption of cadmium ions by different yeast species. Journal of Biosciences, 57(7-8), 634-639.Google Scholar
  20. Burton, J.L., Madsen, S.A., Chang, L.C., Weber, P.S.D., Buckham, K.R., Van Dorp, R., Hickey, M.C., Earley, B., 2005. Gene expression signatures in neutrophils exposed to glucocorticoids: a new paradigm to help explain “neutrophil dysfunction” in parturient dairy cows. Veterinary Immunopathology, 105, 197–219.CrossRefGoogle Scholar
  21. Ceciliani, F., Ceron, J., Eckersley, P.D., Sauerwein, H., 2012. Acute phase proteins in ruminants. Journal of Proteomics, 75, 4207–4231. DOI: Scholar
  22. Chiarla, C., Giovannini, I., Siegel, J.H., 2004.The relationship between plasma cholesterol, amino acids and acute phase proteins in sepsis. Amino Acids, 27:97–100. DOI: Scholar
  23. Conner, J.G., Eckersall, P.D., Doherty, M., Douglas, T.A., 1986. Acute phase response and mastitis in the cow. . Research in Veterinary Science, 41, 126–128.CrossRefGoogle Scholar
  24. Constable P. D., Hinchcliff K. W., Done S. H., Grünberg, W., 2017. Veterinary medicine: a textbook of the diseases of cattle, horses, sheep, pigs, and goats, 11th edn., Elsevier ltd. Veterinary Medicine, 2, 2217–2219.Google Scholar
  25. Dobson, H., Smith, R.F., Royal, M.D., Knight, C.H., Sheldon, I.M., 2007. The high-producing dairy cow and its reproductive performance. Reproduction in Domestic Animals, 42 (Suppl.2), 17–23.CrossRefGoogle Scholar
  26. Dougherty, R.W., Coburn, K.S., Cook, H.M., Allison, M.J., 1975. Preliminary study of appearance of endotoxin in circulatory system of sheep and cattle after induced grain engorgement. American Journal of Veterinary Research, 36(6), 831-832.Google Scholar
  27. Drackley, J.K., 1999. Biology of dairy cows during the transition period: the final frontier. Journal of Dairy Science 82, 2259–2273.CrossRefGoogle Scholar
  28. Drackley, J.K., 2000. Use of NEFA as a Tool to monitor energy balance in transition dairy cows, pp. 1–3. http://www.Livestocktrail.uiuc.Cdu.uploods/dairynet/pp.
  29. Eckel, E.F., Ametaj, B.N., 2016. Role of bacterial endotoxins in the etiopathogenesis of periparturient diseases of transition dairy cows. Journal of Dairy Science 99, 5967–5990. DOI: CrossRefGoogle Scholar
  30. El-Ghmati, S.M., Van Hoeyveld, E.M., Van Strijp, J.G., Ceuppens, J.L., Stevens, E.A., 1996. Identification of haptoglobin as an alternative ligand for CD11b/CD18. Journal of Immunology 156, 2542–2552.Google Scholar
  31. Emmanuel, D.G., Dunn, S.M., Ametaj, B.N., 2008. Feeding high proportions of barley grain stimulates an inflammatory response in dairy cows. Journal of Dairy Science 91, 606–614. DOI: Scholar
  32. Geelen, M.J.H., Wensing, T., 2006. Studies on hepatic lipidosis and coinciding health and fertility problems of high-producing dairy cows using the “Utrecht fatty liver model of dairy cows”. A review. Veterinary Quarterly, 28, 90–104.CrossRefGoogle Scholar
  33. Gozho, G.N., Krause, D.O., Plaizier, J.C., 2007, Ruminal lipopolysaccharide concentration and inflammatory response during grain-induced sub-acute ruminal acidosis in dairy cows, Journal of Dairy Science 90,856–866. DOI:
  34. Grummer, R.R., 1993. Etiology of lipid-related metabolic disorders in periparturient dairy cows. Journal of Dairy Science 76, 3882–3896.CrossRefGoogle Scholar
  35. Grummer, R.R., 1995. Impact of changes in organic nutrient metabolism on feeding the transition dairy cow. Journal of Animal Science, 73, 2820–2833.CrossRefGoogle Scholar
  36. Grummer, R.R., Mashek, D.G., Hayirli, A., 2004. Dry matter intake and energy balance in the transition period. Veterinary Clinics of North America: Food Animal Practice, 20,447–470. DOI: Scholar
  37. Hammon, H.M., Stürmer, G., Schneider, F., Tuchscherer, A., Blum, H., Engelhard, T., Genzel, A., Staufenbiel, R., Kanitz, W., 2009. Performance and metabolic and endocrine changes with emphasis on glucose metabolism in high-yielding dairy cows with high and low fat content in liver after calving. Journal of Dairy Science 92, 1554–1566.CrossRefGoogle Scholar
  38. Herdt, T.H., 2000. Ruminant adaptation to negative energy balance. Influences on the etiology of ketosis and fatty liver. Veterinary Clinics of North America: Food Animal Practice, 16, 215–230. DOI: Google Scholar
  39. Hernández-Castellano, L.E., Hernandez, L.L., Weaver, S., Bruckmaier, R.M., 2016. Increased serum serotonin improves parturient calcium homeostasis in dairy cows. Journal of Dairy Science. 100:1–8 Google Scholar
  40. Horadagoda, N.U., Knox, K.M., Gibbs, H.A., Reid, S.W., Horadagoda, A., Edwards, S.E., Eckersall, P.D., 1999. Acute phase proteins in cattle: discrimination between acute and chronic inflammation. Veterinary Record, 144, 437–441.CrossRefGoogle Scholar
  41. Ingvartsen, 2006. Feeding- and management-related diseases in the transition cow. Animal Feed Science and Technology, 126,175–213. DOI: Scholar
  42. Iranian Council of Animal Care, 1995. Guide to the Care and Use of Experimental Animals, vol. 1 Isfahan University of Technology, Isfahan, Iran.Google Scholar
  43. Khafipour, E., Krause, D.O., Plaizier, J.C., 2009a. A grain-based sub-acute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation. Journal of Dairy Science 92, 1060–1070. DOI: Scholar
  44. Khafipour, E., Krause, D.O., Plaizier, J.C., 2009b. Alfalfa pellet-induced sub-acute ruminal acidosis in dairy cows increases bacterial endotoxin in the rumen without causing inflammation. Journal of Dairy Science 94, 1712–1724. DOI: Scholar
  45. Khafipour, E., Li, S., Plaizier, J. C., Krause, D. O., 2009c. Rumen microbiome composition determined using two nutritional models of sub-acute ruminal acidosis. Applied and Environmental Microbiology, 75, 7115–7124. DOI: Scholar
  46. Lei, C.L., Dong, G.Z., Jin, L., Zhang, S., Zhou, J., 2013. Effects of dietary supplementation of montmorillonite and yeast cell wall on lipopolysaccharide adsorption, nutrient digestibility and growth performance in beef cattle. Livestock Science Journal, 57–63. DOI:
  47. Levels, J.H., Abraham, P.R., Van Den Ende, A., Van Deventer, S.J., 2001. Distribution and kinetics of lipoprotein-bound endotoxin. Infection and Immunity. 69, 2821-2828.CrossRefGoogle Scholar
  48. Li, S., Kroeker, A., Khafipour, E., Rodriguez, J.C., Krause, D.O., Plaizier, J.C., 2010. Effects of sub-acute ruminal acidosis challenges on lipopolysaccharide endotoxin (LPS) in the rumen, cecum, and feces of dairy cows [abstract]. Journal of Animal Science, 88(E-Suppl 2), 433-434. DOI: Scholar
  49. Magata, F., Ishida, Y., Miyamoto, A., Furouka, H., Inokuma, H., Shimizu, T., 2015, Comparison of bacterial endotoxin lipopolysaccharide concentrations in the blood, ovarian follicular fluid and uterine fluid: a clinical case of bovine metritis, Veterinary Medicine and Science, 77(1), 81–84. DOI: Scholar
  50. McCarthy, M., Mann, M.S., Nydam, D.V., Overton, T.R., McArt, J.A.A., 2015. Short communication: concentrations of non-esterified fatty acids and β-hydroxybutyrate in dairy cows are not well correlated during the transition period. Journal of Dairy Science, 98, 6284–6290. DOI: Scholar
  51. McDonald, T.L., Larson, M.A., Mack, D.R., Weber, A., 2001. Elevated extra-hepatic expression and secretion of mammary associated serum amyloid A 3 (M-SAA3) into colostrum. Veterinary Immunology and Immunopathology 83, 203–211.CrossRefGoogle Scholar
  52. Mulligan, F.J., Doherty, M.L., 2008. Production diseases of the transition cow. Veterinary Journal, 176, 3–9.CrossRefGoogle Scholar
  53. Mullins, C.R., Mamedova, L.K., Brouk, M.J., Moore, C.E., Green, H.B., Perfield, K.L., Smith, J.F., Harner, J.P., Bradford, B.J., 2012. Effects of monensin on metabolic parameters, feeding behavior, and productivity of transition dairy cows. Journal of Dairy Science 95, 1323–1336.CrossRefGoogle Scholar
  54. Munford, R.S., Endotoxin(s) and the liver. Gastroenterology, 1978, 75, 532-535.Google Scholar
  55. Murata H., N. Shimada, M. Yoshioka, 2004. Current research on acute phase proteins in veterinary diagnosis: an overview, Vet. J., 168, 28–40.CrossRefGoogle Scholar
  56. Murray H.H., 2000.Traditional and new applications for kaolin, smectite, and palygorskite: a general overview. Applied Clay Science, 17, 207–221.CrossRefGoogle Scholar
  57. National Research Council (NRC), 2001. Nutrient requirements of dairy cattle, 7th revised ed. National Academic Press, Washington, DC.Google Scholar
  58. Nazifi, S., Rezakhani, A., Koohimoghadam, M., Ansari-lari, M., Esmailnezhad, Z., 2008. Evaluation of serum haptoglobin in clinically healthy cattle and cattle with inflammatory diseases in Shiraz, a tropical area in southern Iran. Bulgarian Journal of Veterinary Medicine, 11, NO 2, 95−101.Google Scholar
  59. Nolan J.P., 1975. The role of endotoxin in liver injury. Gastroenterology, 69, 1346-1356.Google Scholar
  60. Nordlund, K. V., Garrett, E. F., Oetzel, G. R., 1995. Herd-based rumenocentesis: a clinical approach to the diagnosis of sub-acute rumen acidosis. Compendium Contin Education Practice Veterinary, 17:s48–s56.Google Scholar
  61. Orrihage, K. E., Sillerstrom, E., Gustafsson, J.A., Nord, C. E., Rafter, J., 1994. Binding of mutagenic heterocyclic amines by intestinal lactic acid bacteria. Mutation Research, 311, 239–248.CrossRefGoogle Scholar
  62. Plaizier, J.C., Krause, D.O., Gozho, G.N., McBride, B.W., 2009. Sub-acute ruminal acidosis in dairy cows: the physiological causes, incidence and consequences. Veterinary Journal, 176, 21-31. DOI: CrossRefGoogle Scholar
  63. Plessers, E., Wyns, H., Watteyn, A., Pardon, B., De Backer, P., Croubels, S., 2015. Characterization of an intravenous lipopolysaccharide inflammation model in calves with respect to the acute-phase response. Veterinary Immunology and Immunopathology, 163, 46–56. DOI: CrossRefGoogle Scholar
  64. Pullen, D.L, Palmquist, D.L, Emery, R.S., 1989. Effect on days of lactation and methionine hydroxyl analog on incorporation of plasma fatty acids into plasma triglycerides. Journal of Dairy Science, 72, 49–58.CrossRefGoogle Scholar
  65. Reid, I.M., Roberts, C.J., 1983. Subclinical fatty liver in dairy cows. Irish Veterinary Journal, 37, 104-110.Google Scholar
  66. Roussel, J.A., Whitney, S.M., Jole, J.D., 1997. Interpreting a bovine serum chemistry profile; part II. Veterinary Medicine,6, 559- 566.Google Scholar
  67. Santos, A., Marquina, D., Leal, J. A., Peinado, J. M., 2000. (166)- B-D-glucan as cell wall receptor for Pichia membranifaciens killer toxin. Applied and Environmental Microbiology, 66, 1809–1813.CrossRefGoogle Scholar
  68. Sevinc, M., Basoglu, A., Oztok, I., Sandikci, M., Birdane, F.M., 1998. The clinical-chemical parameters, serum lipoproteins and fatty infiltration of the liver in ketotic cows. Turkish Journal OF Veterinary and Animal Sciences, 22, 443-447.Google Scholar
  69. Sevinc, M., Basoglu, A., Birdane, F.M., Gokçe, M., Kucukfindik, M., 1999. The changes of metabolic profile in dairy cows during dairy period and after. Turkish Journal OF Veterinary and Animal Sciences, 23, 475-478.Google Scholar
  70. Sevinc, M., Basoglu, A., Birdane, F.M., Boydak, M., 2001, Liver function in dairy cows with fatty liver, Turkish Journal OF Veterinary and Animal Sciences, 152, 4, 297-300.Google Scholar
  71. Spieker, H., 2010. Efficacy of clay minerals and activated charcoal to bind endotoxins in rumen fluid. University of Utrecht, Utrecht, the Nether-lands (Ph.D. thesis).
  72. Takahashi, E., Yuzuka Y., Tanabe, S.Satoh, M.Furouka, H., 2007. Serum amyloid and haptoglobin levels in bovine amyloidosis. Journal of Veterinary Medicine Science, 69(3)-321.323CrossRefGoogle Scholar
  73. Veenhuizen, J.J., Drackley, J.K., Richard, M.J., Sanderson, T.P., Miller, L.D., Young, J.W., 1991. Metabolic changes in blood and liver during development and early treatment of experimental fatty liver and ketosis in cows. Journal of Dairy Science, 74, 4238–4253.CrossRefGoogle Scholar
  74. Wall, S.K., Wellnitz, O., Hernández-Castellano, L.E., Ahmadpour, A., Bruckmaier, R.M., 2016. Supraphysiological oxytocin increases the transfer of immunoglobulins and other blood components to milk during lipopolysaccharide and lipoteichoic acid–induced mastitis in dairy cows. Journal of Dairy Science. 99:1–9, CrossRefGoogle Scholar
  75. Weaver, S.R., Prichard, A.S., Maerz, N.L., Prichard, A.P., Endres, E.L., Hernández-Castellano, L.E., Akins, M.S., Rupert M. Bruckmaier, R.M., Hernandez, L.L., 2017. Elevating serotonin pre-partum alters the Holstein dairy cow hepatic adaptation to lactation. PLoS One, 12(9):e0184939. Doi: CrossRefGoogle Scholar
  76. Yang, F., Haile, D.J., Berger, F.G., Herbert, D.C., Van Beveren, E., Ghio, A.J., 2003. Haptoglobin reduces lung injury associated with exposure to blood. American Journal of Physiology – Lung and Cell Molecular Physiology 284, L402–409.Google Scholar
  77. Zebeli, Q., Ametaj, B.N., 2009. Relationships between rumen lipopolysaccharide and mediators of inflammatory response with milk fat production and efficiency in dairy cows. Journal of Dairy Science, 92, 3800-3809. CrossRefGoogle Scholar
  78. Zebeli, Q., Dunn, S.M. and Ametaj, B.N., 2010. Strong associations among rumen endotoxin and acute phase proteins with plasma minerals in lactating cows fed graded amounts of concentrate. Journal of Animal Science, 88, 1545–1553.Google Scholar
  79. Zerbe, H., Schneider, N., Leibold, W., Wensing, T., Kruip, T. A. M. and Schuberth, H. J., 2000. Altered functional and immunophenotypical properties of neutrophilic granulocytes in postpartum cows associated with fatty liver. Theriogenology, 54, 771–786. DOI:

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Clinical Sciences, School of Veterinary MedicineShiraz UniversityShirazIran
  2. 2.Department of Animal Science, Faculty of AgricultureFerdowsi University of MashhadMashhadIran
  3. 3.School of Veterinary ScienceMassey UniversityPalmerston NorthNew Zealand

Personalised recommendations