Open Access
Research (Published online: 10-06-2018)
8. Astaxanthin inhibits cytokines production and inflammatory gene expression by suppressing IκB kinase-dependent nuclear factor κB activation in pre and postpartum Murrah buffaloes during different seasons
Lakshmi Priyadarshini and Anjali Aggarwal
Veterinary World, 11(6): 782-788

Lakshmi Priyadarshini: Animal Physiology Division, ICAR-National Dairy Research Institute, Karnal - 132 001, Haryana, India.
Anjali Aggarwal: Animal Physiology Division, ICAR-National Dairy Research Institute, Karnal - 132 001, Haryana, India.

doi: 10.14202/vetworld.2018.782-788

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Article history: Received: 23-12-2017, Accepted: 04-05-2018, Published online: 10-06-2018

Corresponding author: Lakshmi Priyadarshini

E-mail: drlpaa@gmail.com

Citation: Priyadarshini L, Aggarwal A (2018) Astaxanthin inhibits cytokines production and inflammatory gene expression by suppressing IκB kinase-dependent nuclear factor κB activation in pre and postpartum Murrah buffaloes during different seasons, Veterinary World, 11(6): 782-788.
Abstract

Aim: We examined regulatory function of astaxanthin on mRNA expression of nuclear factor κB (NF-κB) p65, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in peripheral blood mononuclear cells in pre and postpartum Murrah buffaloes during summer (temperature-humidity index [THI]=86; relative humidity [RH]=24) and winter (THI=58.74; RH=73) seasons.

Materials and Methods: A total of 32 Murrah buffaloes apparently healthy and in their one to four parity were selected from National Dairy Research Institute herd and equally distributed randomly into four groups (control and supplemented groups of buffaloes during summer and winter season, respectively). All groups were fed according to the nutrient requirement of buffaloes (ICAR, 2013). The treatment group was supplemented with astaxanthin at 0.25 mg/kg body weight/animal/day during the period 30 days before expected date of calving and up to 30 days postpartum.

Results: There was downregulation of NF-κB p65 gene in all the groups. NF-κB p65 mRNA expression was lower (p<0.05) in treatment than control group from prepartum to postpartum during summer, while mRNA expression was low only on day 21 after calving during winter season. The mRNA expression of IL-6, TNF-α, and IFN-γ was lower (p<0.05) in treatment than a control group of buffaloes during summer and winter seasons. The mRNA expression of NF-κB p65, IL-6, TNF-α, and IFN-γ was higher (p<0.05) in summer than in winter seasons.

Conclusion: The xanthophyll carotenoid astaxanthin a reddish-colored C-40 compound is a powerful broad-ranging antioxidant that naturally occurs in a wide variety of living organisms, such as microalgae, fungi, crustaceans, and complex plants. Astaxanthin blocked nuclear translocation of NF-κB p65 subunit and IκBa degradation, which correlated with its inhibitory effect on IκB kinase (IKK) activity. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking NF-κB activation and as a consequent suppression of IKK activity and IκB-degradation.

Keywords: astaxanthin, Murrah buffalo, nuclear factor κB p65, summer, winter.

References

1. Qin, S., Liu, G.X. and Hu, Z.Y. (2008) The accumulation and metabolism of astaxanthin in Scenedesmus obliquus. Process Biochem., 43: 795-802. [Crossref]

2. Zhao, Z.W., Cai, W., Lin, Y.L., Lin, Q.F., Jiang, Q., Lin, Z. and Chen, L.L. (2011) Ameliorative effect of astaxanthin on endothelial dysfunction in streptozotocin-induced diabetes in male rats. Arzneimittelforschung, 61: 239-246. [Crossref] [PubMed]

3. Boussiba, S., Cohen, Z., Richmond, A. and Vonshak, A. (2000) Procedure for Large-Scale Production of Astaxanthin from Haematococcus. PCT Patents 9, 728, 274.

4. Choi, H.D., Kang, H.E., Yang, S.H., Lee, M.G. and Shin, W.G. (2011) Pharmacokinetics and first-passetabolism of astaxanthin in rats. Br. J. Nutr., 105: 220-227. [Crossref] [PubMed]

5. Aoi, W., Naito, Y., Takanami, Y., Ishii, T., Kawai, Y., Akagiri, S., Kato, Y., Osawa, T. and Yoshikawa, T. (2008) Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPTI modification. Biochem. Biophys. Res. Commun., 366: 892-897. [Crossref] [PubMed]

6. Derosa, G., Limas, C.P., Macias, P.C., Estrella, A. and Maffioli, P. (2014) Dietary and nutraceutical approach to Type 2 diabetes. Arch. Med. Sci., 10: 336-344. [Crossref] [PubMed] [PMC]

7. Kavitha, K., Kowshik, J., Kishore, T.K., Baba, A.B. and Nagini, S. (2013) Astaxanthin inhibits NF-kappaB and Wnt/beta-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochem. Biophys. Acta, 1830: 4433-4444. [Crossref] [PubMed]

8. Palazzo, L., Thomas, B., Jemth, A.S., Coldy, T., Leidecker, O., Feijs, K.L.H., Zaja, R., Loseva, O., Puigvert, J.C., Matic, I., Helleday, T. and Ahel, I. (2015) Processing of protein ADP-ribosylation by nudix hydrolases. Biochem. J., 468(2): 293-301. [Crossref] [PubMed]

9. Wolf, A.M., Asoh, S., Hiranuma, H., Ohsawa, I., Iio, K., Satou, A., Ishikura, M. and Ohta, S. (2010) Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress. J. Nutr. Biochem., 21(5): 381-389. [Crossref] [PubMed]

10. Sahebkar, A., Serban, C., Ursoniu, S. and Banach, M. (2015) Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials. J. Funct. Foods, 18: 898-909. [Crossref]

11. Lauver, D.A., Driscoll, E.M. and Lucchesi, B.R. (2008) Disodium disuccinate astaxanthin prevents carotid artery rethrombosis and ex vivo platelet activation. Pharmacology, 82: 67-73. [Crossref] [PubMed]

12. Gross, G.J. and Lockwood, S.F. (2004) Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative. Life Sci., 75: 215-224. [Crossref] [PubMed]

13. Hussein, G., Goto, H., Oda, S., Sankawa, U., Matsumoto, K. and Watanabe, H. (2006) Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats. Biol. Pharm. Bull., 29: 684-688. [Crossref]

14. Banach, M., Serban, C., Aronow, W.S., Rvsz, J., Dragan, S., Lerma, E.V., Apetrii, M. and Covic, A. (2014) Lipid, blood pressure and kidney update. Int. Urol. Nephrol., 46: 947-961. [Crossref] [PubMed] [PMC]

15. Baeuerle, P.A. and Baichwal, V.R. (1997) NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol., 65: 111-137. [Crossref]

16. Dale, E., Davis, M. and Faustman, D.L. (2006) A role for transcription factor NF-kappaB in autoimmunity: Possible interactions of genes, sex, and the immune response. Adv. Physiol. Educ., 30: 152-158. [Crossref] [PubMed]

17. Li, N. and Karin, M. (1999) Is NF-kB the sensor of oxidative stress? FASEB J., 13: 1137-1143. [Crossref] [PubMed]

18. Castrillo, A., de Las, H.B., Hortelano, S., Rodriguez, B., Villar, A. and Bosca, L. (2001) Inhibition of the nuclear factor kappa B (NF-κB) pathway by tetracyclic kaurene diterpenes in macrophages. Specific effects on NF-?B-inducing kinase activity and on the coordinate activation of ERK and p38 MAPK. J. Biol. Chem., 276: 15854-15860. [Crossref] [PubMed]

19. Keifer, J.A., Guttridge, D.C., Ashburner, B.P. and Baldwin, A.S. Jr. (2001) Inhibition of NF-?B activity by thalidomide through suppression of I?B kinase activity. J. Biol. Chem., 276: 22382-22387. [Crossref] [PubMed]

20. Ghosh, S. and Hayden, M.S. (2008) New regulators of NF-kB in inflammation. Nat. Rev. Immunol., 8: 837-848. [Crossref] [PubMed]

21. Romagnoli, M., Gomez-Cabrera, M.C., Perrelli, M.G., Biasi, F., Pallardo, F.V., Sastre, J., Poli, G. and Vina, J. (2010) Xanthine oxidase-induced oxidative stress causes activation of NF-kappaB and inflammation in the liver of type I diabetic rats. Free Radic. Biol. Med., 49(2): 171-177. [Crossref] [PubMed]

22. Hybertson, B.M., Gao, B., Bose, S.K. and McCord, J.M. (2011) Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation. Mol. Aspects. Med., 32: 234-246. [Crossref] [PubMed]

23. Pedernera, M., Celi, P., Garcia, S.C., Salvin, H.E., Barchia, I. and Fulkerson, W.J. (2010) Effect of diet, energy balance and milk production on oxidative stress in early-lactating dairy cows grazing pasture. Vet. J., 186: 352-357. [Crossref] [PubMed]

24. Kim, H., Na, H.J., Kim, C.K., Kim, Y., Ha, K.S., Lee, H., Chung, H.T., Kwon, H.J., Kwon, Y.G. and Kim, Y.M. (2008) The non-provitamin a carotenoid, lutein, inhibits NF-?B dependent gene expression through redox-based regulation of the phosphatidylinositol 3 kinase/PTEN/Akt and NF-?B-inducing kinase pathways: Role of H2O2 in NF-?B activation. ?Free Radic. Biol. Med., 45: 885-896. [Crossref]

25. Lignell, A. and Inborr, J. Method of the Prophylactic Treatment of Mastitis. United State Patent US 6335015 B1, January 1, 2002.

26. Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT. Method, 25(4): 402-408. [Crossref] [PubMed]

27. Li, D., Song, J.Z., Li, H., Shan, M.H., Liang, Y., Zhu, J. and Xie, Z. (2015) Storage lipid synthesis is necessary for autophagy induced by nitrogen starvation. FEBS Lett., 589(2): 269-276. [Crossref] [PubMed]

28. Lee, S.J., Bai, S.K., Lee, K.S., Namkoong, S., Na, H.J., Ha, K.S., Han, J.A., Yim, S.V., Chang, K., Kwon, Y.G., Lee, S.K. and Kim, Y.M. (2003) Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I-kappaB kinase-dependent NF-kappaB activation. Mol. Cells, 16: 97-105. [PubMed]

29. Kishimoto, Y., Tani, M., Uto-Kondo, H., Iizuka, M., Saita, E., Sone, H., Kurata, H. and Kondo, K. (2010) Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages. Eur. J. Nutr., 49: 119-126. [Crossref] [PubMed]

30. Macedo, R.C., Bolin, A.P., Marin, D.P. and Otton, R. (2010) Astaxanthin addition improves human neutrophils function: In vitro study. Eur. J. Nutr., 49: 447-457. [Crossref] [PubMed]

31. Speranza, L., Pesce, M., Patruno, A., Franceschelli, S., de Lutiis, M.A., Grilli, A. and Felaco, M. (2012) Astaxanthin treatment reduced oxidative induced pro-inflammatory cytokines secretion in U937: SHP-1 as a novel biological target. Mar. Drugs, 10(4): 890-899. [Crossref] [PubMed] [PMC]

32. Kishimoto, Y., Yoshida, H. and Kondo, K. (2016) Potential anti-atherosclerotic properties of astaxanthin. Mar. Drugs, 14(35): 1-13. [Crossref]

33. Contreras, G.A., Kirkwood, R.N. and Sordillo, L.M. (2013) Mononuclear leukocyte fatty acid composition and inflammatory phenotype in periparturient and lactating sows. J. Anim. Sci., 91: 174-187. [Crossref] [PubMed]

34. Ohgami, K., Shiratori, K., Kotake, S., Nishida, T., Mizuki, N., Yazawa, K. and Ohno, S. (2003) Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Invest. Ophthalmol. Vis. Sci., 44(6): 2694-2701. [Crossref]

35. Patra, M.K., Kumar, H. and Nandi, S. (2013) Neutrophil functions and cytokines expression profile in buffaloes with impending postpartum reproductive disorders. Asian Aust. J. Anim. Sci., 26(10): 1406-1415. [Crossref] [PubMed] [PMC]

36. Takahashi, K., Takimoto, T., Sato, K. and Akiba, Y. (2011) Effect of dietary supplementation of astaxanthin from phaffiarhodozyma on lipopolysaccharide-induced early inflammatory responses in male broiler chickens (Gallus gallus) fed a corn-enriched diet. Anim. Sci. J., 82(6): 753-758. [Crossref] [PubMed]