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Dietary Zinc Oxide Modulates Antioxidant Capacity, Small Intestine Development, and Jejunal Gene Expression in Weaned Piglets

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Abstract

The current study was conducted to investigate the effects of dietary zinc oxide (ZnO) on the antioxidant capacity, small intestine development, and jejunal gene expression in weaned piglets. Ninety-six 21-day-old piglets were randomly assigned to three dietary treatments. Each treatment had eight replicates with four piglets per replicate. The piglets were fed either control diet (control) or control diet supplemented with in-feed antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) or pharmacological doses of ZnO (3000 mg/kg). The experiment lasted 4 weeks. Blood samples were collected at days 14 and 28, while intestinal samples were harvested at day 28 of the experiment. Dietary high doses of ZnO supplementation significantly increased the body weight (BW) at day 14 and average daily gain (ADG) of days 1 to 14 in weaned piglets, when compared to control group (P < 0.05). The incidence of diarrhea of piglets fed ZnO-supplemented diets, at either days 1 to 14, days 14 to 28, or the overall experimental period, was significantly decreased in comparison with those in other groups (P < 0.05). Supplementation with ZnO increased the villus height of the duodenum and ileum in weaned piglets and decreased the crypt depth of the duodenum, when compared to the other groups (P < 0.05). Dietary ZnO supplementation decreased the malondialdehyde (MDA) concentration at either day 14 or day 28, but increased total superoxide dismutase (T-SOD) at day 14, when compared to that in the control (P < 0.05). ZnO supplementation upregulated the messenger RNA (mRNA) expression of zonula occludens-1 (ZO-1) and occludin in the jejunum mucosa of weaned piglets, compared to those in the control (P < 0.05). The pro-inflammatory cytokine interleukin-lβ (IL-1β) mRNA expression in the jejunum mucosa was downregulated in the ZnO-supplemented group, compared with the control (P < 0.05). Both in-feed antibiotics and ZnO supplementation decreased the mRNA expression of interferon-γ (IFN-γ), but increased the mRNA expression of transforming growth factor-β (TGF-β), in the jejunum mucosa of piglets, when compared to those in the control (P < 0.05). In summary, supplemental ZnO was effective on the prevention of post-weaning diarrhea (PWD) in weaned piglets and showed comparative growth-promoting effect on in-feed antibiotics, probably by the mechanism of improvement of the antioxidant capacity, restoration of intestinal barrier function and development, and modulation of immune functions.

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References

  1. Sales J (2013) Effects of pharmacological concentrations of dietary zinc oxide on growth of post-weaning pigs: a meta-analysis. Biol Trace Elem Res 152:343–349

    Article  CAS  PubMed  Google Scholar 

  2. Pluske JR (2013) Feed- and feed additives-related aspects of gut health and development in weanling pigs. J Anim Sci Biotechnol 4:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Heo JM, Opapeju FO, Pluske JR, Kim JC, Hampson DJ, Nyachoti CM (2013) Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds. J Anim Physiol Anim Nutr (Berl) 97:207–237

    Article  CAS  Google Scholar 

  4. Carlson MS, Hill GM, Link JE (1999) Early- and traditionally weaned nursery pigs benefit from phase-feeding pharmacological concentrations of zinc oxide: effect on metallothionein and mineral concentrations. J Anim Sci 77:1199–1207

    Article  CAS  PubMed  Google Scholar 

  5. Hill GM, Mahan DC, Carter SD, Cromwell GL, Ewan RC, Harrold RL, Lewis AJ, Miller PS, Shurson GC, Veum TL, Nutrition NCRCoS (2001) Effect of pharmacological concentrations of zinc oxide with or without the inclusion of an antibacterial agent on nursery pig performance. J Anim Sci 79:934–941

    Article  CAS  PubMed  Google Scholar 

  6. Case CL, Carlson MS (2002) Effect of feeding organic and inorganic sources of additional zinc on growth performance and zinc balance in nursery pigs. J Anim Sci 80:1917–1924

    Article  CAS  PubMed  Google Scholar 

  7. Ou D, Li D, Cao Y, Li X, Yin J, Qiao S, Wu G (2007) Dietary supplementation with zinc oxide decreases expression of the stem cell factor in the small intestine of weanling pigs. J Nutr Biochem 18:820–826

    Article  CAS  PubMed  Google Scholar 

  8. Zhang B, Guo Y (2009) Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets. Brit J Nutr 102:687

    Article  CAS  PubMed  Google Scholar 

  9. NRC (2012) Nutrient requirements of swine. Natl. Acad. Press, Washington, D.C

    Google Scholar 

  10. Zhu C, Wu Y, Jiang Z, Zheng C, Wang L, Yang X, Ma X, Gao K, Hu Y (2015) Dietary soy isoflavone attenuated growth performance and intestinal barrier functions in weaned piglets challenged with lipopolysaccharide. Int Immunopharmacol 28(1):288–294

    Article  CAS  PubMed  Google Scholar 

  11. Hahn JD, Baker DH (1993) Growth and plasma zinc responses of young pigs fed pharmacologic levels of zinc. J Anim Sci 71:3020–3024

    CAS  PubMed  Google Scholar 

  12. Azawal S, Black RE, Bhan MK, Handari N, Sinha A, Jalla S (1995) Zinc supplementation in young children with acute diarrhea in India. N Engl J Med 333:839–844

    Article  Google Scholar 

  13. Lazzerini M, Ronfani L (2008) Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev 6:CD005436

    Google Scholar 

  14. Chai W, Zakrzewski SS, Gunzel D, Pieper R, Wang Z, Twardziok S, Janczyk P, Osterrieder N, Burwinkel M (2014) High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets. BMC Vet Res 10:75

    Article  PubMed  PubMed Central  Google Scholar 

  15. O’Shea CJ, McAlpine P, Sweeney T, Varley PF, O'Doherty JV (2014) Effect of the interaction of seaweed extracts containing laminarin and fucoidan with zinc oxide on the growth performance, digestibility and faecal characteristics of growing piglets. Br J Nutr 111:798–807

    Article  PubMed  Google Scholar 

  16. Hedemann MS, Hojsgaard S, Jensen BB (2003) Small intestinal morphology and activity of intestinal peptidases in piglets around weaning. J Anim Physiol Anim Nutr (Berl) 87:32–41

    Article  CAS  Google Scholar 

  17. Ruan Z, Liu S, Zhou Y, Mi S, Liu G, Wu X, Yao K, Assaad H, Deng Z, Hou Y, Wu G, Yin Y (2014) Chlorogenic acid decreases intestinal permeability and increases expression of intestinal tight junction proteins in weaned rats challenged with LPS. PLoS One 9:e97815

    Article  PubMed  PubMed Central  Google Scholar 

  18. Xiong X, Yang H, Tan B, Yang C, Wu M, Liu G, Kim SW, Li T, Li L, Wang J, Wu G, Yin Y (2015) Differential expression of proteins involved in energy production along the crypt-villus axis in early-weaning pig small intestine. Am J Physiol Gastrointest Liver Physiol 309:G229–G237

    Article  CAS  PubMed  Google Scholar 

  19. Xiong X, Yang H, Hu X, Wang X, Li B, Long L, Li T, Wang J, Hou Y, Wu G, Yin Y (2016) Differential proteome analysis along jejunal crypt-villus axis in piglets. Front Biosci (Landmark Ed) 21:343–363

    Article  Google Scholar 

  20. Li X, Yin J, Li D, Chen X, Zang J, Zhou X (2006) Dietary supplementation with zinc oxide increases Igf-I and Igf-I receptor gene expression in the small intestine of weanling piglets. J Nutr 136:1786–1791

    CAS  PubMed  Google Scholar 

  21. Li BT, van Kessel AG, Caine WR, Huang SX, Kirkwood RN (2001) Small intestinal morphology and bacterial populations in ileal digesta and feces of newly weaned pigs receiving a high dietary level of zinc oxide. Can J Anim Sci 81:511–516

    Article  CAS  Google Scholar 

  22. Pie S, Lalles JP, Blazy F, Laffitte J, Seve B, Oswald IP (2004) Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. J Nutr 134:641–647

    CAS  PubMed  Google Scholar 

  23. Wijtten PJ, van der Meulen J, Verstegen MW (2011) Intestinal barrier function and absorption in pigs after weaning: a review. Br J Nutr 105:967–981

    Article  CAS  PubMed  Google Scholar 

  24. Kansagra K, Stoll B, Rognerud C, Niinikoski H, Ou CN, Harvey R, Burrin D (2003) Total parenteral nutrition adversely affects gut barrier function in neonatal piglets. Am J Physiol Gastrointest Liver Physiol 285:G1162–G1170

    Article  CAS  PubMed  Google Scholar 

  25. Sturniolo GC, Fries W, Mazzon E, Di Leo V, Barollo M, D'Inca R (2002) Effect of zinc supplementation on intestinal permeability in experimental colitis. J Lab Clin Med 139:311–315

    Article  CAS  PubMed  Google Scholar 

  26. Roy SK, Behrens RH, Haider R, Akramuzzaman SM, Mahalanabis D, Wahed MA, Tomkins AM (1992) Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. J Pediatr Gastroenterol Nutr 15:289–296

    Article  CAS  PubMed  Google Scholar 

  27. Wapnir RA (2000) Zinc deficiency, malnutrition and the gastrointestinal tract. J Nutr 130:1388S–1392S

    CAS  PubMed  Google Scholar 

  28. Hennig B, Wang Y, Ramasamy S, McClain CJ (1992) Zinc deficiency alters barrier function of cultured porcine endothelial cells. J Nutr 122:1242–1247

    CAS  PubMed  Google Scholar 

  29. Liu P, Pieper R, Rieger J, Vahjen W, Davin R, Plendl J, Meyer W, Zentek J (2014) Effect of dietary zinc oxide on morphological characteristics, mucin composition and gene expression in the colon of weaned piglets. PLoS One 9:e91091

    Article  PubMed  PubMed Central  Google Scholar 

  30. Roselli M, Finamore A, Garaguso I, Britti MS, Mengheri E (2003) Zinc oxide protects cultured enterocytes from the damage induced by Escherichia coli. J Nutr 133:4077–4082

    CAS  PubMed  Google Scholar 

  31. Sargeant HR, Miller HM, Shaw MA (2011) Inflammatory response of porcine epithelial IPEC J2 cells to enterotoxigenic E. coli infection is modulated by zinc supplementation. Mol Immunol 48:2113–2121

    Article  CAS  PubMed  Google Scholar 

  32. Ren W, Duan J, Yin J, Liu G, Cao Z, Xiong X, Chen S, Li T, Yin Y, Hou Y, Wu G (2014) Dietary L-glutamine supplementation modulates microbial community and activates innate immunity in the mouse intestine. Amino Acids 46:2403–2413

    Article  CAS  PubMed  Google Scholar 

  33. Hennig B, Wang Y, Ramasamy S, McClain CJ (1993) Zinc protects against tumor necrosis factor-induced disruption of porcine endothelial cell monolayer integrity. J Nutr 123:1003–1009

    CAS  PubMed  Google Scholar 

  34. Sargeant HR, McDowall KJ, Miller HM, Shaw MA (2010) Dietary zinc oxide affects the expression of genes associated with inflammation: transcriptome analysis in piglets challenged with ETEC K88. Vet Immunol Immunopathol 137:120–129

    Article  CAS  PubMed  Google Scholar 

  35. Srivastava RC, Farookh A, Ahmad N, Misra M, Hasan SK, Husain MM (1995) Reduction of cis-platinum induced nephrotoxicity by zinc histidine complex: the possible implication of nitric oxide. Biochem Mol Biol Int 36:855–862

    CAS  PubMed  Google Scholar 

  36. Yin J, Ren W, Liu G, Duan J, Yang G, Wu L, Li T, Yin Y (2013) Birth oxidative stress and the development of an antioxidant system in newborn piglets. Free Radic Res 47:1027–1035

    Article  CAS  PubMed  Google Scholar 

  37. Yin J, Wu MM, Xiao H, Ren WK, Duan JL, Yang G, Li TJ, Yin YL (2014) Development of an antioxidant system after early weaning in piglets. J Anim Sci 92:612–619

    Article  CAS  PubMed  Google Scholar 

  38. Yin J, Duan JL, Cui ZJ, Ren WK, Li TJ, Yin YL (2015) Hydrogen peroxide-induced oxidative stress activates NF-κB and Nrf2/Keap1 signals and triggers autophagy in piglets. RSC Adv 5:15479–15486

    Article  CAS  Google Scholar 

  39. Wang X, Ou D, Yin J, Wu G, Wang J (2009) Proteomic analysis reveals altered expression of proteins related to glutathione metabolism and apoptosis in the small intestine of zinc oxide-supplemented piglets. Amino Acids 37:209–218

    Article  PubMed  Google Scholar 

  40. Foster M, Samman S (2010) Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid Redox Signal 13:1549–1573

    Article  CAS  PubMed  Google Scholar 

  41. Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P (1997) Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 43:1209–1214

    CAS  PubMed  Google Scholar 

  42. Boshi Y, Nezu R, Cui L, Chen K, Khan J, Yoshida H, Sando K, Kamata S, Takagi Y, Okada A (1996) Adhesive mucous gel layer and mucus release as intestinal barrier in rats. J Parenter Enter Nutr 20:98–104

    Article  Google Scholar 

  43. Hedemann MS, Jensen BB, Poulsen HD (2006) Influence of dietary zinc and copper on digestive enzyme activity and intestinal morphology in weaned pigs. J Anim Sci 84:3310–3320

    Article  CAS  PubMed  Google Scholar 

  44. Liu P, Pieper R, Tedin L, Martin L, Meyer W, Rieger J, Plendl J, Vahjen W, Zentek J (2014) Effect of dietary zinc oxide on jejunal morphological and immunological characteristics in weaned piglets. J Anim Sci 92:5009–5018

    Article  CAS  PubMed  Google Scholar 

  45. Slade RD, Kyriazakis I, Carroll SM, Reynolds FH, Wellock IJ, Broom LJ, Miller HM (2011) Effect of rearing environment and dietary zinc oxide on the response of group-housed weaned pigs to enterotoxigenic Escherichia coli O149 challenge. Animal 5:1170–1178

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge the financial supports provided by the National Natural Science Foundation of China (31501967; 31472112), the China Agriculture Research System (CARS-36), the National Science and Technology Support Program (2012BAD39B01-5), the Special Fund for Agro-scientific Research in the Public Interest (201403047), the Operating Funds for Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition (2014B030301054), the Science and Technology Program of Guangdong Province, China (2016B070701013), and the Hundred Outstanding Talents Training Program at Guangdong Province, China.

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Authors and Affiliations

  1. Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science (South China), Guangdong Public Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China

    Cui Zhu, Hang Lv, Li Wang & Zongyong Jiang

  2. Agro-biological Gene Research Center, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, China

    Cui Zhu, Hang Lv, Zhuang Chen, Xiuju Wu, Zhongjian Chen, Weina Zhang, Rui Liang & Zongyong Jiang

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  1. Cui Zhu
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  2. Hang Lv
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Correspondence to Zongyong Jiang.

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The procedures of the experiment were approved by the Animal Care and Use Committee of Guangdong Academy of Agricultural Sciences, China.

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The authors declare that they have no conflict of interests.

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Cui Zhu and Hang Lv contributed equally to the work.

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Zhu, C., Lv, H., Chen, Z. et al. Dietary Zinc Oxide Modulates Antioxidant Capacity, Small Intestine Development, and Jejunal Gene Expression in Weaned Piglets. Biol Trace Elem Res 175, 331–338 (2017). https://doi.org/10.1007/s12011-016-0767-3

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  • DOI: https://doi.org/10.1007/s12011-016-0767-3

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