Recently, astaxanthin (ASTA) studies have focused on several biological functions such as radical scavenging, singlet oxygen quenching, anti-carcinogenesis, anti-diabetic, anti-obesity, anti-inflammatory, anti-melanogenesis, and immune enhancement activities. In this study, we investigated the potential role protective of ASTA, an antioxidant marine carotenoid, in restoring physiological conditions in U937 cells stimulated with LPS (10 μg/ml). Our results show that pre-treatment with ASTA (10 μM) for 1 h attenuates the LPS-induced toxicity and ROS production. The beneficial effect of ASTA is associated with a reduction intracellular O2？ production by restoring the antioxidant network activity of superoxide dismutase (SOD) and catalase (CAT), which influence HO-1 expression and activity by inhibiting nuclear translocation of Nrf2. We accordingly hypothesize that ASTA has therapeutic properties protecting U937 cells from LPS-induced inflammatory and oxidative stress.
References
[1]
Paiva SA, Russell RM (1999) Beta-carotene and other carotenoids as antioxidants. J Am Coll Nutr 18(5): 426–33. doi: 10.1080/07315724.1999.10718880
[2]
Riccioni G, Speranza L, Pesce M, Cusenza S, D'Orazio N, et al. (2012) Novel phytonutrient contributors to antioxidant protection against cardiovascular disease. Nutrition 28(6): 605–10. doi: 10.1016/j.nut.2011.11.028
[3]
Riccioni G, D'Orazio N, Salvatore C, Franceschelli S, Pesce M, et al. (2012) Carotenoids and vitamins C and E in the prevention of cardiovascular disease. Int J Vitam Nutr Res 82(1): 15–26. doi: 10.1024/0300-9831/a000090
[4]
Riccioni G, D'Orazio N, Franceschelli S, Speranza L (2011) Marine carotenoids and cardiovascular risk markers. Mar Drugs 9(7): 1166–75. doi: 10.3390/md9071166
[5]
Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, et al. (2002) Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 61(3): 554–61. Erratum in: Mol Pharmacol 61(5): 1264. doi: 10.1124/mol.61.3.554
[6]
Vomhof-Dekrey EE, Picklo Sr MJ (2012) The Nrf2-antioxidant response element pathway:a target for regulating energy metabolism. J Nutr Biochem 23(10): 1201–6. doi: 10.1016/j.jnutbio.2012.03.005
[7]
Speranza L, Pesce M, Franceschelli S, Mastrangelo F, Patruno A, et al. (2012) The role of inducible nitric oxide synthase and haemoxygenase 1 in growth and development of dental tissue'. Cell Biochem Funct 30(3): 217–23. doi: 10.1002/cbf.1838
[8]
Grilli A, De Lutiis MA, Patruno A, Speranza L, Gizzi F, et al. (2003) Inducible nitric oxide synthase and heme oxygenase-1 in rat heart: direct effect of chronic exposure to hypoxia. Ann Clin Lab Sci 33(2): 208–15.
[9]
Li N, Alam J, Venkatesan MI, Eiguren-Fernandez A, Schmitz D, et al. (2004) Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals. J Immunol 173(5): 3467–81. doi: 10.4049/jimmunol.173.5.3467
[10]
Dr？ge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1): 47–95.
[11]
Patruno A, Franceschelli S, Pesce M, Maccallini C, Fantacuzzi M, et al. (2012) Novel aminobenzyl-acetamidine derivatives modulate the differential regulation of NOSs in LPS induced inflammatory response: role of PI3K/Akt pathway. Biochim Biophys Acta 1820(12): 2095–104. doi: 10.1016/j.bbagen.2012.08.014
[12]
Speranza L, Pesce M, Franceschelli S, Bucciarelli T, Gallina S, et al. (2013) The biological evaluation of ADMA/SDMA and eNOS in patients with ACHF. Front Biosci (Elite Ed) 5: 551–7. doi: 10.2741/e637
[13]
Franceschelli S, Pesce M, Vinciguerra I, Ferrone A, Riccioni G, et al. (2011) Licocalchone-C extracted from Glycyrrhizaglabra inhibits lipopolysaccharide-interferon-γ inflammation by improving antioxidantconditions and regulating inducible nitric oxide synthase expression. Molecules 16(7): 5720–34. doi: 10.3390/molecules16075720
[14]
Speranza L, Franceschelli S, Pesce M, Reale M, Menghini L, et al. (2010) Antiinflammatory effects in THP-1 cells treated with verbascoside. Phytother Res 24(9): 1398–404. doi: 10.1002/ptr.3173
[15]
Patruno A, Amerio P, Pesce M, Vianale G, Di Luzio S, et al. (2010) Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing. Br J Dermatol 162(2): 258–66. doi: 10.1111/j.1365-2133.2009.09527.x
[16]
Speranza L, Pesce M, Patruno A, Franceschelli S, De Lutiis MA, et al. (2012) Astaxanthin treatment reduced oxidative induced pro-inflammatory cytokines secretion in U937: SHP-1 as a novel biological target. Mar Drugs 10(4): 890–9. doi: 10.3390/md10040890
[17]
Babior BM (2000) Phagocytes and oxidative stress. Am J Med109(1): 33–44. doi: 10.1016/s0002-9343(00)00481-2
[18]
Elferink J (1984) Measurement of the metabolic burst in human neutrophils: a comparison between cytochrome c and NBT reduction. Res Commun Chem Pathol Pharmacol 43(2): 339–342.
[19]
Speranza L, Franceschelli S, Pesce M, Vinciguerra I, De Lutiis MA, et al. (2008) Phosphodiesterase type-5 inhibitor and oxidative stress. Int J Immunopathol Pharmacol 21(4): 879–89.
[20]
Speranza L, Franceschelli S, Riccioni G, Di Nicola M, Ruggeri B, et al. (2012) BNP and iNOS in decompensated chronic heart failure: a linear correlation. Front Biosci (Elite Ed) 4: 1255–62. doi: 10.2741/e456
[21]
Miao L, St Clair DK (2009) Regulation of superoxide dismutase genes: implications in disease. Free Radic Biol Med47(4): 344–56. doi: 10.1016/j.freeradbiomed.2009.05.018
[22]
Sun Y, Oberley LW (1996) Redox regulation of transcriptional activators Free Radic Biol Med. 21: 335–348. doi: 10.1016/0891-5849(96)00109-8
[23]
Ryter SW, Alam J, Choi AM (2006) Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 86(2): 583–650. doi: 10.1152/physrev.00011.2005
[24]
Kurata S, Matsumoto M, Tsuji Y, Nakajima H (1996) Lipopolysaccharide activates transcription of the hemeoxygenase gene in mouse M1 cells through oxidative activation of nuclear factor kappa B. Eur J Biochem. 239: 566–571. doi: 10.1111/j.1432-1033.1996.0566u.x
[25]
Cheng HW, Lee KC, Cheah KP, Chang ML, Lin CW, et al. (2013) Polygonumviviparum L. inhibits the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through haeme oxygenase-1 induction and activation of the Nrf2 pathway. J Sci Food Agric 93: 491–7. doi: 10.1002/jsfa.5795
[26]
Itoh K, Mochizuki M, Ishii Y, Ishii T, Shibata T, et al. (2004) Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-Delta(12,14)-prostaglandin j(2). Mol Cell Biol24(1): 36–45. doi: 10.1128/mcb.24.1.36-45.2004
[27]
He X, Ma Q (2009) NRF2 cysteine residues are critical for oxidant/electrophile-sensing, Kelch-like ECH-associated protein-1-dependent ubiquitination-proteasomal degradation, and transcription activation. Mol Pharmacol 76(6): 1265–78. doi: 10.1124/mol.109.058453
[28]
Ryter SW, Choi AM (2009) Heme oxygenase-1/carbon monoxide: from metabolism to molecular therapy. Am J Respir Cell Mol Biol 41(3): 251–60. doi: 10.1165/rcmb.2009-0170tr
[29]
Barbagallo I, Galvano F, Frigiola A, Cappello F, Riccioni G, et al. (2013) Potential therapeutic effects of natural heme oxygenase-1 inducers in cardiovascular diseases. Antioxid Redox Signal 18(5): 507–21. doi: 10.1089/ars.2011.4360
[30]
Iarlori C, Gambi D, Lugaresi A, Patruno A, Felaco M, et al. (2008) Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone). Mult Scler 4(6): 739–48. doi: 10.1177/1352458508088918
[31]
Stahl W, Sies H (2003) Antioxidant activity of carotenoids. Mol Aspects Med24(6): 345–51. doi: 10.1016/s0098-2997(03)00030-x
[32]
Miyashita K (2009) Function of marine carotenoids. Forum Nutr 61: 136–46. doi: 10.1159/000212746
