The effects of chitosan on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) activity and gene expression in vivo or vitro were investigated in weaned piglets. In vivo, 180 weaned piglets were assigned to five dietary treatments with six replicates. The piglets were fed on a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. In vitro, the peripheral blood mononuclear cells (PBMCs) from a weaned piglet were cultured respectively with 0 (control), 40, 80, 160, and 320 µg chitosan/ml medium. Results showed that serum NO concentrations on days 14 and 28 and iNOS activity on day 28 were quadratically improved with increasing chitosan dose (P < 0.05). The iNOS mRNA expressions were linearly or quadratically enhanced in the duodenum on day 28, and were improved quadratically in the jejunum on days 14 and 28 and in the ileum on day 28 (P < 0.01). In vitro, the NO concentrations, iNOS activity, and mRNA expression in unstimulated PBMCs were quadratically enhanced by chitosan, but the improvement of NO concentrations and iNOS activity by chitosan were markedly inhibited by N-(3-[aminomethyl] benzyl) acetamidine (1400w) (P < 0.05). Moreover, the increase of NO concentrations, iNOS activity, and mRNA expression in PBMCs induced by lipopolysaccharide (LPS) were suppressed significantly by chitosan (P < 0.05). The results indicated that the NO concentrations, iNOS activity, and mRNA expression in piglets were increased by feeding chitosan in a dose-dependent manner. In addition, chitosan improved the NO production in unstimulated PBMCs but inhibited its production in LPS-induced cells, which exerted bidirectional regulatory effects on the NO production via modulated iNOS activity and mRNA expression.
Angel L. (2008): Role of nitric oxide in the gastrointestinal tract. Arthritis Research and Therapy, 10 (Suppl. 2), S4.
Bogdan C. (2001): Nitric oxide and the immune response. Nature Immunology, 2, 907–916. https://doi.org/10.1038/ni1001-907
Bosi P., Merialdi G., Scandurra S., Messori S., Bardasi L., Nisi I., Russo D., Casini L., Trevisi P. (): Feed supplemented with 3 different antibiotics improved food intake and decreased the activation of the humoral immune response in healthy weaned pigs but had differing effects on intestinal microbiota. Journal of Animal Science, 89, 4043-4053 https://doi.org/10.2527/jas.2010-3311
Chou Tz-Chong, Fu Earl, Shen E-Chin (2003): Chitosan inhibits prostaglandin E2 formation and cyclooxygenase-2 induction in lipopolysaccharide-treated RAW 264.7 macrophages. Biochemical and Biophysical Research Communications, 308, 403-407 https://doi.org/10.1016/S0006-291X(03)01407-4
David O.S., Jason S.C., Joshua D.N., Adam J.F. (2012): The potential of nitric oxide releasing therapies as antimicrobial agents. Landes Bioscience, 33, 271–279.
Deng Xingzhao, Li Xiaojing, Liu Pai, Yuan Shulin, Zang Jianjun, Li Songyu, Piao Xiangshu (2008): Effect of Chito-oligosaccharide Supplementation on Immunity in Broiler Chickens. Asian-Australasian Journal of Animal Sciences, 21, 1651-1658 https://doi.org/10.5713/ajas.2008.80056
Feng Jie, Zhao Luhang, Yu Qiqi (2004): Receptor-mediated stimulatory effect of oligochitosan in macrophages. Biochemical and Biophysical Research Communications, 317, 414-420 https://doi.org/10.1016/j.bbrc.2004.03.048
Geerts S., Gryseels B. (2000): Drug Resistance in Human Helminths: Current Situation and Lessons from Livestock. Clinical Microbiology Reviews, 13, 207-222 https://doi.org/10.1128/CMR.13.2.207-222.2000
Hwang Shiaw-Min, Chen Chiung-Yun, Chen Shan-Shan, Chen Jian-Chyi (2000): Chitinous Materials Inhibit Nitric Oxide Production by Activated RAW 264.7 Macrophages. Biochemical and Biophysical Research Communications, 271, 229-233 https://doi.org/10.1006/bbrc.2000.2602
Johnson Ian R., Ball Ron O., Baracos Vickie E., Field Catherine J. (2006): Glutamine supplementation influences immune development in the newly weaned piglet. Developmental & Comparative Immunology, 30, 1191-1202 https://doi.org/10.1016/j.dci.2006.03.003
Livak Kenneth J., Schmittgen Thomas D. (2001): Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25, 402-408 https://doi.org/10.1006/meth.2001.1262
Li H. Y., Yan S. M., Shi B. L., Guo X. Y. (2009): Effect of Chitosan on Nitric Oxide Content and Inducible Nitric Oxide Synthase Activity in Serum and Expression of Inducible Nitric Oxide Synthase mRNA in Small Intestine of Broiler Chickens. Asian-Australasian Journal of Animal Sciences, 22, 1048-1053 https://doi.org/10.5713/ajas.2009.80708
Liu Li, Yuan Zhengrong, Chen Cui, Zhang Limin, Chen Xiaojie, Liu Xidong, Gao Xue, Li Junya, Gao Huijiang, Zhang Lupei, Xu Shangzhong (2012): Inflammatory Response of Peripheral Blood Mononuclear Cells Post Intramammary Challenge with Staphylococcus aureus in Dairy Cows. Journal of Animal and Veterinary Advances, 11, 2588-2593 https://doi.org/10.3923/javaa.2012.2588.2593
Barton Mary D. (2000): Antibiotic use in animal feed and its impact on human healt. Nutrition Research Reviews, 13, 279- https://doi.org/10.1079/095442200108729106
Mesko Bertalan, Poliska Szilard, Nagy Laszlo (2011): Gene expression profiles in peripheral blood for the diagnosis of autoimmune diseases. Trends in Molecular Medicine, 17, 223-233 https://doi.org/10.1016/j.molmed.2010.12.004
Nathan C.F., Stuehr D.J. (1990): Does endothelium-derived nitric oxide have a role in cytokine-induced hypotension? Journal of the National Cancer Institute, 82, 726–728.
NRC (1998): Nutrient Requirements of Swine. 10th Ed. The National Academies Press, Washington, USA.
Peluso Gianfranco, Petillo Orsolina, Ranieri Marilena, Santin Matteo, Ambrosic Luigi, Calabró Daniela, Avallone Bice, Balsamo Giuseppe (1994): Chitosan-mediated stimulation of macrophage function. Biomaterials, 15, 1215-1220 https://doi.org/10.1016/0142-9612(94)90272-0
Pie S., Lalles J.P., Blazy F., Lafﬁtte J., Seve B., Oswald I.P. (2004): Weaning is associated with an up regulation of expression of inflammatory cytokines in the intestine of piglets. Journal of Nutrition, 134, 641–647.
Porporatto Carina, Bianco Ismael D, Riera Clelia M, Correa Silvia G (2003): Chitosan induces different l-arginine metabolic pathways in resting and inflammatory macrophages. Biochemical and Biophysical Research Communications, 304, 266-272 https://doi.org/10.1016/S0006-291X(03)00579-5
Porporatto C. (2005): Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration. Journal of Leukocyte Biology, 78, 62-69 https://doi.org/10.1189/jlb.0904541
Shi B.L. (2004): Effects of chitosan on growth performance and immune function in broilers and the underlying mechanisms. Ph.D. Thesis, Beijing: China Agricultural University.
Synowiecki Józef, Al-Khateeb Nadia Ali (2003): Production, Properties, and Some New Applications of Chitin and Its Derivatives. Critical Reviews in Food Science and Nutrition, 43, 145-171 https://doi.org/10.1080/10408690390826473
Tripathi Parul, Tripathi Prashant, Kashyap Luv, Singh Vinod (2007): The role of nitric oxide in inflammatory reactions. FEMS Immunology & Medical Microbiology, 51, 443-452 https://doi.org/10.1111/j.1574-695X.2007.00329.x
Xing Z., Schat K. A. (2000): Inhibitory Effects of Nitric Oxide and Gamma Interferon on In Vitro and In Vivo Replication of Marek's Disease Virus. Journal of Virology, 74, 3605-3612 https://doi.org/10.1128/JVI.74.8.3605-3612.2000
Xu Yuanqing, Shi Binlin, Yan Sumei, Li Tiyu, Guo Yiwei, Li Junliang (2013): Effects of Chitosan on Body Weight Gain, Growth Hormone and Intestinal Morphology in Weaned Pigs. Asian-Australasian Journal of Animal Sciences, 26, 1484-1489 https://doi.org/10.5713/ajas.2013.13085
Yang Eun-Jin, Kim Jong-Gwan, Kim Ji-Young, Kim Seong, Lee Nam, Hyun Chang-Gu (2010): Anti-inflammatory effect of chitosan oligosaccharides in RAW 264.7 cells. Open Life Sciences, 5, - https://doi.org/10.2478/s11535-009-0066-5
Yin Y.-L., Tang Z. R., Sun Z. H., Liu Z. Q., Li T. J., Huang R. L., Ruan Z., Deng Z. Y., Gao B., Chen L. X., Wu G. Y., Kim S. W. (2008): Effect of Galacto-mannan-oligosaccharides or Chitosan Supplementation on Cytoimmunity and Humoral Immunity in Early-weaned Piglets. Asian-Australasian Journal of Animal Sciences, 21, 723-731 https://doi.org/10.5713/ajas.2008.70408
Yu Zhijun, Zhao Luhang, Ke Haiping (2004): Potential role of nuclear factor-kappaB in the induction of nitric oxide nd tumor necrosis factor-alpha by oligochitosan in macrophages. International Immunopharmacology, 4, 193-200 https://doi.org/10.1016/j.intimp.2003.12.001
Zhao L.H. (2004): Oligochitosan induces NO production via NF-Kb in macrophages. Ph.D. Thesis, Hangzhou: Zhejiang University.