Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review
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Muflihatul Muniroh
Abstract
The exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.
Research funding: None declared.
Conflict of interest: The author has declared no conflict of interest.
Author contributions: Author has accepted responsibility for the entire content of this manuscript and approved its submission.
Informed consent: Not applicable.
Ethical approval: Not applicable.
References
1. ATSDR. Atsdr’s substance priority list. Agency for Toxic Substances and Disease Registry; 2019. Available from: https://www.atsdr.cdc.gov/spl/.Suche in Google Scholar
2. UNEP&WHO. Guidance for identifiying populations at risk from mercury exposure. United States: Inter-Organization Programme for the Sound Management of Chemicals (IOMC); 2008.Suche in Google Scholar
3. United Nations Environment Programme, World Health Organization, International Labour Organisation, Commission of the European Communities, and International Program on Chemical Safety. Environmental health criteria. volumes. Geneva: World Health Organization; 1976.Suche in Google Scholar
4. ATSDR. Toxicological profile for mercury. Agency for Toxic Substances and Disease Registry; 1999. Available from: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=115&tid=24.Suche in Google Scholar
5. WHO. Mercury and health. World Health Organization; 2017. Available from: https://www.who.int/en/news-room/fact-sheets/detail/mercury-and-health.Suche in Google Scholar
6. Bjorkman, L, Lundekvam, BF, Laegreid, T, Bertelsen, BI, Morild, I, Lilleng, P, et al. Mercury in human brain, blood, muscle and toenails in relation to exposure: an autopsy study. Environ Health 2007;6:30. https://doi.org/10.1186/1476-069x-6-30.Suche in Google Scholar
7. Clarkson, TW, Vyas, JB, Ballatori, N. Mechanisms of mercury disposition in the body. Am J Ind Med 2007;50:757–64. https://doi.org/10.1002/ajim.20476.Suche in Google Scholar
8. EPA. Mercury study report to congress. United State Environmental Protection Agency; 1997. Available from: https://www.epa.gov/mercury/mercury-study-report-congress.Suche in Google Scholar
9. Mahaffey, KR, Clickner, RP, Bodurow, CC. Blood organic mercury and dietary mercury intake: National Health and Nutrition Examination Survey, 1999 and 2000. Environ Health Perspect 2004;112:562–70. https://doi.org/10.1289/ehp.6587.Suche in Google Scholar
10. Grandjean, P, White, RF, Weihe, P, Jorgensen, PJ. Neurotoxic risk caused by stable and variable exposure to methylmercury from seafood. Ambul Pediatr 2003;3:18–23. https://doi.org/10.1367/1539-4409(2003)003<0018:nrcbsa>2.0.co;2.10.1367/1539-4409(2003)003<0018:NRCBSA>2.0.CO;2Suche in Google Scholar
11. Madejczyk, MS, Aremu, DA, Simmons-Willis, TA, Clarkson, TW, Ballatori, N. Accelerated urinary excretion of methylmercury following administration of its antidote N-Acetylcysteine requires Mrp2/Abcc2, the apical multidrug resistance-associated protein. J Pharmacol Exp Ther 2007;322:378–84. https://doi.org/10.1124/jpet.107.122812.Suche in Google Scholar
12. Muniroh, M, Khan, N, Koriyama, C, Akiba, S, Vogel, CF, Yamamoto, M. Suppression of methylmercury-Induced Il-6 and Mcp-1 expressions by N-Acetylcysteine in U-87mg human astrocytoma cells. Life Sci 2015;134:16–21. https://doi.org/10.1016/j.lfs.2015.04.024.Suche in Google Scholar
13. Yokoo, EM, Valente, JG, Grattan, L, Schmidt, SL, Platt, I, Silbergeld, EK. Low level methylmercury exposure affects neuropsychological function in adults. Environ Health 2003;2:8–1. https://doi.org/10.1186/1476-069x-2-8.Suche in Google Scholar
14. Aremu, DA, Madejczyk, MS, Ballatori, N. N-Acetylcysteine as a potential antidote and biomonitoring agent of methylmercury exposure. Environ Health Perspect 2008;116:26–31. https://doi.org/10.1289/ehp.10383.Suche in Google Scholar
15. Falluel-Morel, A, Lin, L, Sokolowski, K, McCandlish, E, Buckley, B, DiCicco-Bloom, E. N-Acetyl cysteine treatment reduces mercury-induced neurotoxicity in the developing rat hippocampus. J Neurosci Res 2012;90:743–50. https://doi.org/10.1002/jnr.22819.Suche in Google Scholar
16. Godefroy, D, Gosselin, RD, Yasutake, A, Fujimura, M, Combadiere, C, Maury-Brachet, R, et al. The Chemokine CCl2 protects against methylmercury neurotoxicity. Toxicol Sci 2012;125:209–18. https://doi.org/10.1093/toxsci/kfr252.Suche in Google Scholar
17. Hwang, GW, Lee, JY, Ryoke, K, Matsuyama, F, Kim, JM, Takahashi, T, et al. Gene expression profiling using DNA microarray analysis of the cerebellum of mice treated with methylmercury. J Toxicol Sci 2011;36:389–91. https://doi.org/10.2131/jts.36.389.Suche in Google Scholar PubMed
18. Takahashi, T, Iwai-Shimada, M, Syakushi, Y, Kim, M-S, Hwang, G-W, Miura, N, et al. Methylmercury induces expression of Interleukin-1β and Interleukin-19 in mice brains. Fundam Toxicol Sci 2015;2:239–43. https://doi.org/10.2131/fts.2.239.Suche in Google Scholar
19. Wu, Q, Li, WK, Zhou, ZP, Li, YY, Xiong, TW, Du, YZ, et al. The Tibetan medicine zuotai differs from HgCl2 and MeHg in producing liver injury in mice. Regul Toxicol Pharmacol 2016;78:1–7. https://doi.org/10.1016/j.yrtph.2016.03.017.Suche in Google Scholar PubMed
20. Chen, YW, Huang, CF, Tsai, KS, Yang, RS, Yen, CC, Yang, CY, et al. The role of phosphoinositide 3-Kinase/Akt signaling in low-dose mercury-induced mouse pancreatic beta-cell dysfunction in vitro and in vivo. Diabetes 2006;55:1614–24. https://doi.org/10.2337/db06-0029.Suche in Google Scholar PubMed
21. Ni, M, Li, X, Rocha, JB, Farina, M, Aschner, M. Glia and methylmercury neurotoxicity. J Toxicol Environ Health A 2012;75:1091–101. https://doi.org/10.1080/15287394.2012.697840.Suche in Google Scholar PubMed PubMed Central
22. Chang, JY, Tsai, PF. Il-6 Release from mouse glia caused by MeHg requires cytosolic phospholipase A2 activation. Neurosci Lett 2009;461:85–9. https://doi.org/10.1016/j.neulet.2009.06.004.Suche in Google Scholar PubMed PubMed Central
23. Garg, TK, Chang, JY. 15-Deoxy-Delta 12, 14-prostaglandin J2 prevents reactive oxygen species generation and mitochondrial membrane depolarization induced by oxidative stress. BMC Pharmacol 2004;4:6. https://doi.org/10.1186/1471-2210-4-6.Suche in Google Scholar PubMed PubMed Central
24. Farina, M, Aschner, M, Rocha, JB. Oxidative stress in MeHg-induced neurotoxicity. Toxicol Appl Pharmacol 2011;256:405–17. https://doi.org/10.1016/j.taap.2011.05.001.Suche in Google Scholar PubMed PubMed Central
25. David, J, Nandakumar, A, Muniroh, M, Akiba, S, Yamamoto, M, Koriyama, C. Suppression of methylmercury-induced Mip-2 expression by N-Acetyl-L-Cysteine in murine Raw264.7 macrophage cell line. Eur J Med Res 2017;22:45. https://doi.org/10.1186/s40001-017-0287-4.10.1186/s40001-017-0287-4Suche in Google Scholar PubMed PubMed Central
26. Yamamoto, M, Khan, N, Muniroh, M, Motomura, E, Yanagisawa, R, Matsuyama, T, et al. Activation of Interleukin-6 and -8 expressions by methylmercury in human U937 macrophages involves Rela and P50. J Appl Toxicol 2017;37:611–20. https://doi.org/10.1002/jat.3411.Suche in Google Scholar PubMed
27. Bassett, T, Bach, P, Chan, HM. Effects of methylmercury on the secretion of pro-inflammatory cytokines from primary microglial cells and astrocytes. Neurotoxicology 2012;33:229–34. https://doi.org/10.1016/j.neuro.2011.10.003.Suche in Google Scholar PubMed
28. Muniroh, M, Gumay, AR, Indraswari, DA, Bahtiar, Y, Hardian, H, Bakri, S, et al. Activation of Mip-2 and Mcp-5 expression in methylmercury-exposed mice and their suppression by N-Acetyl-L-Cysteine. Neurotox Res 2020;37:827–34. https://doi.org/10.1007/s12640-020-00174-4.Suche in Google Scholar PubMed
29. Kim, MS, Takahashi, T, Lee, JY, Hwang, GW, Naganuma, A. Methylmercury induces CCl2 expression through activation of Nf-Kappab in human 1321n1 astrocytes. J Toxicol Sci 2012;37:1275–8. https://doi.org/10.2131/jts.37.1275.Suche in Google Scholar PubMed
30. Chang, JY. Methylmercury-induced Il-6 release requires phospholipase C activities. Neurosci Lett 2011;496:152–6. https://doi.org/10.1016/j.neulet.2011.04.004.Suche in Google Scholar PubMed PubMed Central
31. Chang, JY. Methylmercury causes Glial Il-6 release. Neurosci Lett 2007;416:217–20. https://doi.org/10.1016/j.neulet.2007.01.076.Suche in Google Scholar PubMed
32. Takanaga, H, Yoshitake, T, Hara, S, Yamasaki, C, Kunimoto, M. cAMP- induced astrocytic differentiation of C6 glioma cells is mediated by autocrine Interleukin-6. J Biol Chem 2004;279:15441–7. https://doi.org/10.1074/jbc.M311844200.Suche in Google Scholar PubMed
33. Shanker, G, Aschner, JL, Syversen, T, Aschner, M. Free radical formation in cerebral cortical astrocytes in culture induced by methylmercury. Brain Res Mol Brain Res 2004;128:48–57. https://doi.org/10.1016/j.molbrainres.2004.05.022.Suche in Google Scholar PubMed
34. Samuni, Y, Goldstein, S, Dean, OM, Berk, M. The chemistry and biological activities of N-Acetylcysteine. BBA – Gen Subjects 2013;1830:4117–29. https://doi.org/10.1016/j.bbagen.2013.04.016.Suche in Google Scholar PubMed
35. Ballatori, N, Lieberman, MW, Wang, W. N-Acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect 1998;106:267–71. https://doi.org/10.1289/ehp.98106267.Suche in Google Scholar PubMed PubMed Central
36. Yuntao, F, Chenjia, G, Panpan, Z, Wenjun, Z, Suhua, W, Guangwei, X, et al. Role of autophagy in methylmercury-induced neurotoxicity in rat primary astrocytes. Arch Toxicol 2016;90:333–45. https://doi.org/10.1007/s00204-014-1425-1.Suche in Google Scholar PubMed PubMed Central
37. Ballatori, N. Transport of toxic metals by molecular mimicry. Environ Health Perspect 2002;110(5 Suppl):689–94. https://doi.org/10.1289/ehp.02110s5689.Suche in Google Scholar PubMed PubMed Central
38. Kruh, GD, Belinsky, MG. The MRP family of drug efflux pumps. Oncogene 2003;22:7537–52. https://doi.org/10.1038/sj.onc.1206953.Suche in Google Scholar PubMed
39. Kaur, P, Aschner, M, Syversen, T. Glutathione modulation influences methyl mercury induced neurotoxicity in primary cell cultures of neurons and astrocytes. Neurotoxicology 2006;27:492–500. https://doi.org/10.1016/j.neuro.2006.01.010.Suche in Google Scholar PubMed
40. Erickson, MA, Hansen, K, Banks, WA. Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood-brain barrier: protection by the antioxidant N-Acetylcysteine. Brain Behav Immun 2012;26:1085–94. https://doi.org/10.1016/j.bbi.2012.07.003.Suche in Google Scholar PubMed PubMed Central
41. Garg, TK, Chang, JT, Banks, WA. Methylmercury causes oxidative stress and cytotoxicity in microglia: attenuation by 15-deoxy-delta 12, 14-Prostaglandin. J2. J. Neuroimmunol 2006;171:17–28. https://doi.org/10.1016/j.jneuroim.2005.09.007.Suche in Google Scholar PubMed
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Assessing and mitigating environmental exposures in early life
- Mini Reviews
- Impact of pesticide exposure in childhood
- Risk of Mercury exposure during childhood: a review of Sri Lankan situation
- Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review
- Multi-level analysis of symptoms of poison exposure reported to the Japanese Poison Information Center
- Review Article
- Chemical mixtures and neurobehavior: a review of epidemiologic findings and future directions
- Original Articles
- Human health risk assessment of heavy metals via consumption of fish from Kao Bay
- The relationship of mercury exposure with neurological problems in artisanal gold in Makassar city
- Contribution of house dust contamination towards lead exposure among children in Karachi, Pakistan
- Concentration of folic acid (FA) in serum of Japanese pregnant women
- Introducing the ORIGINS project: a community-based interventional birth cohort
- Effect of particulate matter 2.5 exposure to urinary malondialdehyde levels of public transport drivers in Jakarta
Artikel in diesem Heft
- Frontmatter
- Editorial
- Assessing and mitigating environmental exposures in early life
- Mini Reviews
- Impact of pesticide exposure in childhood
- Risk of Mercury exposure during childhood: a review of Sri Lankan situation
- Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review
- Multi-level analysis of symptoms of poison exposure reported to the Japanese Poison Information Center
- Review Article
- Chemical mixtures and neurobehavior: a review of epidemiologic findings and future directions
- Original Articles
- Human health risk assessment of heavy metals via consumption of fish from Kao Bay
- The relationship of mercury exposure with neurological problems in artisanal gold in Makassar city
- Contribution of house dust contamination towards lead exposure among children in Karachi, Pakistan
- Concentration of folic acid (FA) in serum of Japanese pregnant women
- Introducing the ORIGINS project: a community-based interventional birth cohort
- Effect of particulate matter 2.5 exposure to urinary malondialdehyde levels of public transport drivers in Jakarta
