Skip to main content
SpringerLink
Log in

Curcumin Alleviates Arsenic Trioxide–Induced Inflammation and Pyroptosis via the NF-κB/NLRP3 Signaling Pathway in the Hypothalamus of Ducks

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Arsenic (As) as a neurotoxic environmental pollutant has attracted extensive attention. Curcumin (Cur) is a natural antioxidant that shows an excellent protective effect against arsenic trioxide (ATO)–induced toxicity in many animal organs. However, the mechanism of Cur against ATO-induced hypothalamic toxicity in ducks has not yet been fully elucidated. Here, ducks were treated with ATO and/or Cur during 28 days; the results showed that ATO exposure induced growth retardation, messy feathers, and abnormal posture in ducks. Moreover, ATO caused neuron vacuolar degeneration and disintegration in the hypothalamus of ducks. Simultaneously, ATO induced blood–brain barrier damage, downregulated the expression of ZO-1, Occludin, and mediated NF‐κB activation, resulting in an increase in inflammatory factors (TLR-4, NF-κB, TNF-α, IL-2, and IL-6). Furthermore, ATO increased the production of pyroptosis-related factors (Caspase-1, IL-18, IL-1), exacerbating the inflammatory damage through NLRP3-mediated inflammasome activation. Cur, on the other hand, exerted excellent inhibitory effects on inflammation and pyroptosis. In summary, our study revealed that ATO triggered inflammation and pyroptosis by modulating NF-κB/NLRP3 signaling pathways in the hypothalamus of ducks, and Cur can alleviate inflammation and pyroptosis caused by ATO. Therefore, as a plant extract, Cur has the potential to prevent and cure ATO-induced hypothalamus toxicity.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Jiang X, Yu W, Wu S, Tang L, Zhong G, Wan F, Lan J, Zhang H, Pan J, Tang Z, Zhang X, Hu L, Huang R (2021) Arsenic (III) and/or Antimony (III) induced disruption of calcium homeostasis and endoplasmic reticulum stress resulting in apoptosis in mice heart. Ecotoxicol Environ Saf 220:112394. https://doi.org/10.1016/j.ecoenv.2021.112394

    Article  CAS  PubMed  Google Scholar 

  2. Das HK, Mitra AK, Sengupta PK, Hossain A, Islam F, Rabbani GH (2004) Arsenic concentrations in rice, vegetables, and fish in Bangladesh: a preliminary study. Environ Int 30(3):383–387. https://doi.org/10.1016/j.envint.2003.09.005

    Article  CAS  PubMed  Google Scholar 

  3. Karri V, Schuhmacher M, Kumar V (2016) Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: a general review of metal mixture mechanism in brain. Environ Toxicol Pharmacol 48:203–213. https://doi.org/10.1016/j.etap.2016.09.016

    Article  CAS  PubMed  Google Scholar 

  4. Shao YZ, Zhao HJ, Wang Y, Liu JJ, Li JL, Luo LY, Xing MW (2018) The apoptosis in arsenic-induced oxidative stress is associated with autophagy in the testis tissues of chicken. Poult Sci 97(9):3248–3257. https://doi.org/10.3382/ps/pey156

    Article  CAS  PubMed  Google Scholar 

  5. Moon KA, Oberoi S, Barchowsky A, Chen Y, Guallar E, Nachman KE, Rahman M, Sohel N, D’Ippoliti D, Wade TJ, James KA, Farzan SF, Karagas MR, Ahsan H, Navas-Acien A (2018) A dose-response meta-analysis of chronic arsenic exposure and incident cardiovascular disease. Int J Epidemiol 47(3):1013. https://doi.org/10.1093/ije/dyy073

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhong G, Wan F, Lan J, Jiang X, Wu S, Pan J, Tang Z, Hu L (2021) Arsenic exposure induces intestinal barrier damage and consequent activation of gut-liver axis leading to inflammation and pyroptosis of liver in ducks. Sci Total Environ 788:147780. https://doi.org/10.1016/j.scitotenv.2021.147780

    Article  CAS  PubMed  Google Scholar 

  7. Sharma A, Kumar S (2019) Arsenic exposure with reference to neurological impairment: an overview. Rev Environ Health 34(4):403–414. https://doi.org/10.1515/reveh-2019-0052

    Article  CAS  PubMed  Google Scholar 

  8. Garza-Lombo C, Pappa A, Panayiotidis MI, Gonsebatt ME, Franco R (2019) Arsenic-induced neurotoxicity: a mechanistic appraisal. J Biol Inorg Chem 24(8):1305–1316. https://doi.org/10.1007/s00775-019-01740-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Adlanmerini M, Nguyen HC, Krusen BM, Teng CW, Geisler CE, Peed LC, Carpenter BJ, Hayes MR, Lazar MA (2021) Hypothalamic REV-ERB nuclear receptors control diurnal food intake and leptin sensitivity in diet-induced obese mice. J Clin Invest 131(1) https://doi.org/10.1172/JCI140424

  10. Cui T, Jiang W, Yang F, Luo J, Hu R, Cao H, Hu G, Zhang C (2021) Molybdenum and cadmium co-induce hypothalamus toxicity in ducks via disturbing Nrf2-mediated defense response and triggering mitophagy. Ecotoxicol Environ Saf 228:113022. https://doi.org/10.1016/j.ecoenv.2021.113022

    Article  CAS  PubMed  Google Scholar 

  11. Prakash C, Soni M, Kumar V (2016) Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: a review. J Appl Toxicol 36(2):179–188. https://doi.org/10.1002/jat.3256

    Article  CAS  PubMed  Google Scholar 

  12. Yu S, Fu L, Lu J, Wang Z, Fu W (2020) Xiao-Yao-San reduces blood-brain barrier injury induced by chronic stress in vitro and vivo via glucocorticoid receptor-mediated upregulation of Occludin. J Ethnopharmacol 246:112165. https://doi.org/10.1016/j.jep.2019.112165

    Article  CAS  PubMed  Google Scholar 

  13. Daneman R, Prat A (2015) The blood-brain barrier. Cold Spring Harb Perspect Biol 7(1):a20412. https://doi.org/10.1101/cshperspect.a020412

    Article  Google Scholar 

  14. Wu S, Rao G, Wang R, Pang Q, Zhang X, Huang R, Li T, Tang Z, Hu L (2021) The neuroprotective effect of curcumin against ATO triggered neurotoxicity through Nrf2 and NF-kappaB signaling pathway in the brain of ducks. Ecotoxicol Environ Saf 228:112965. https://doi.org/10.1016/j.ecoenv.2021.112965

    Article  CAS  PubMed  Google Scholar 

  15. Adedara IA, Abiola MA, Adegbosin AN, Odunewu AA, Farombi EO (2019) Impact of binary waterborne mixtures of nickel and zinc on hypothalamic-pituitary-testicular axis in rats. Chemosphere 237:124501. https://doi.org/10.1016/j.chemosphere.2019.124501

    Article  CAS  PubMed  Google Scholar 

  16. Wang C, Nie G, Yang F, Chen J, Zhuang Y, Dai X, Liao Z, Yang Z, Cao H, Xing C, Hu G, Zhang C (2020) Molybdenum and cadmium co-induce oxidative stress and apoptosis through mitochondria-mediated pathway in duck renal tubular epithelial cells. J Hazard Mater 383:121157. https://doi.org/10.1016/j.jhazmat.2019.121157

    Article  CAS  PubMed  Google Scholar 

  17. Wang X, Cao H, Fang Y, Bai H, Chen J, Xing C, Zhuang Y, Guo X, Hu G, Yang F (2022) Activation of endoplasmic reticulum-mitochondria coupling drives copper-induced autophagy in duck renal tubular epithelial cells. Ecotoxicol Environ Saf 235:113438. https://doi.org/10.1016/j.ecoenv.2022.113438

    Article  CAS  PubMed  Google Scholar 

  18. Moeini A, Torrecilla S, Tovar V, Montironi C, Andreu-Oller C, Peix J, Higuera M, Pfister D, Ramadori P, Pinyol R, Sole M, Heikenwalder M, Friedman SL, Sia D, Llovet JM (2019) An immune gene expression signature associated with development of human hepatocellular carcinoma identifies mice that respond to chemopreventive agents. Gastroenterology 157(5):1383–1397. https://doi.org/10.1053/j.gastro.2019.07.028

    Article  CAS  PubMed  Google Scholar 

  19. Baldwin AJ (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649–683. https://doi.org/10.1146/annurev.immunol.14.1.649

    Article  CAS  PubMed  Google Scholar 

  20. Kwon DJ, Bae YS, Ju SM, Youn GS, Choi SY, Park J (2014) Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-kappaB and JNK activation in RAW 264.7 macrophages. Bmb Rep 47(6):318–323. https://doi.org/10.5483/bmbrep.2014.47.6.200

    Article  PubMed  PubMed Central  Google Scholar 

  21. Deng M, Guo H, Tam JW, Johnson BM, Brickey WJ, New JS, Lenox A, Shi H, Golenbock DT, Koller BH, Mckinnon KP, Beutler B, Ting JP (2019) Platelet-activating factor (PAF) mediates NLRP3-NEK7 inflammasome induction independently of PAFR. J Exp Med 216(12):2838–2853. https://doi.org/10.1084/jem.20190111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bertheloot D, Latz E, Franklin BS (2021) Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 18(5):1106–1121. https://doi.org/10.1038/s41423-020-00630-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gaul S, Leszczynska A, Alegre F, Kaufmann B, Johnson CD, Adams LA, Wree A, Damm G, Seehofer D, Calvente CJ, Povero D, Kisseleva T, Eguchi A, Mcgeough MD, Hoffman HM, Pelegrin P, Laufs U, Feldstein AE (2021) Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis. J Hepatol 74(1):156–167. https://doi.org/10.1016/j.jhep.2020.07.041

    Article  CAS  PubMed  Google Scholar 

  24. Vallee A, Lecarpentier Y (2020) Curcumin and endometriosis. Int J Mol Sci 21(7). https://doi.org/10.3390/ijms21072440

  25. Abdel-Daim MM, El-Tawil OS, Bungau SG, Atanasov AG (2019) Applications of antioxidants in metabolic disorders and degenerative diseases: mechanistic approach. Oxid Med Cell Longev 2019:4179676. https://doi.org/10.1155/2019/4179676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Salehi B, Stojanovic-Radic Z, Matejic J, Sharifi-Rad M, Anil KN, Martins N, Sharifi-Rad J (2019) The therapeutic potential of curcumin: a review of clinical trials. Eur J Med Chem 163:527–545. https://doi.org/10.1016/j.ejmech.2018.12.016

    Article  CAS  PubMed  Google Scholar 

  27. Bahrami A, Sathyapalan T, Moallem SA, Sahebkar A (2020) Counteracting arsenic toxicity: curcumin to the rescue? J Hazard Mater 400:123160. https://doi.org/10.1016/j.jhazmat.2020.123160

    Article  CAS  PubMed  Google Scholar 

  28. Lan J, Tang L, Wu S, Huang R, Zhong G, Jiang X, Tang Z, Hu L (2022) Curcumin alleviates arsenic-induced injury in duck skeletal muscle via regulating the PINK1/Parkin pathway and protecting mitochondrial function. Toxicol Appl Pharmacol 434:115820. https://doi.org/10.1016/j.taap.2021.115820

    Article  CAS  PubMed  Google Scholar 

  29. Wu S, Yu W, Jiang X, Huang R, Zhang X, Lan J, Zhong G, Wan F, Tang Z, Hu L (2021) Protective effects of curcumin on ATO-induced nephrotoxicity in ducks in relation to suppressed autophagy, apoptosis and dyslipidemia by regulating oxidative stress. Ecotoxicol Environ Saf 219:112350. https://doi.org/10.1016/j.ecoenv.2021.112350

    Article  CAS  PubMed  Google Scholar 

  30. Mochizuki H (2019) Arsenic neurotoxicity in humans. Int J Mol Sci 20(14). https://doi.org/10.3390/ijms20143418

  31. Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51(2):257–281. https://doi.org/10.1016/j.freeradbiomed.2011.04.008

    Article  CAS  PubMed  Google Scholar 

  32. Li X, Yi H, Wang H (2018) Sulphur dioxide and arsenic affect male reproduction via interfering with spermatogenesis in mice. Ecotoxicol Environ Saf 165:164–173. https://doi.org/10.1016/j.ecoenv.2018.08.109

    Article  CAS  PubMed  Google Scholar 

  33. Piao Y, Liu Y, Xie X (2013) Change trends of organ weight background data in Sprague Dawley rats at different ages. J Toxicol Pathol 26(1):29–34. https://doi.org/10.1293/tox.26.29

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhao Y, Zhuang Y, Shi Y, Xu Z, Zhou C, Guo L, Liu P, Wu C, Hu R, Hu G, Guo X, Xu L (2021) Effects of N-acetyl-l-cysteine on heat stress-induced oxidative stress and inflammation in the hypothalamus of hens. J Therm Biol 98:102927. https://doi.org/10.1016/j.jtherbio.2021.102927

    Article  CAS  PubMed  Google Scholar 

  35. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37(1):13–25. https://doi.org/10.1016/j.nbd.2009.07.030

    Article  CAS  PubMed  Google Scholar 

  36. Bao L, Shi H (2010) Arsenite induces endothelial cell permeability increase through a reactive oxygen species-vascular endothelial growth factor pathway. Chem Res Toxicol 23(11):1726–1734. https://doi.org/10.1021/tx100191t

    Article  CAS  PubMed  Google Scholar 

  37. Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M (2016) Curcumin and health. Molecules 21(3):264. https://doi.org/10.3390/molecules21030264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Didonato JA, Mercurio F, Karin M (2012) NF-kappaB and the link between inflammation and cancer. Immunol Rev 246(1):379–400. https://doi.org/10.1111/j.1600-065X.2012.01099.x

    Article  CAS  PubMed  Google Scholar 

  39. Leitner GR, Wenzel TJ, Marshall N, Gates EJ, Klegeris A (2019) Targeting Toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders. Expert Opin Ther Targets 23(10):865–882. https://doi.org/10.1080/14728222.2019.1676416

    Article  CAS  PubMed  Google Scholar 

  40. Opal SM, Depalo VA (2000) Anti-inflammatory cytokines. Chest 117(4):1162–1172. https://doi.org/10.1378/chest.117.4.1162

    Article  CAS  PubMed  Google Scholar 

  41. Zhang K, Zhao P, Guo G, Guo Y, Tian L, Sun X, Li S, He Y, Sun Y, Chai H, Zhang W, Xing M (2016) Arsenic trioxide attenuates NF-kappaB and cytokine mRNA levels in the livers of cocks. Biol Trace Elem Res 170(2):432–437. https://doi.org/10.1007/s12011-015-0455-8

    Article  CAS  PubMed  Google Scholar 

  42. Zhong W, Qian K, Xiong J, Ma K, Wang A, Zou Y (2016) Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-kappaB related signaling. Biomed Pharmacother 83:302–313. https://doi.org/10.1016/j.biopha.2016.06.036

    Article  CAS  PubMed  Google Scholar 

  43. Zhang J, Zheng Y, Luo Y, Du Y, Zhang X, Fu J (2019) Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/ TLR4/ NF-kappaB pathways in BV2 cells. Mol Immunol 116:29–37. https://doi.org/10.1016/j.molimm.2019.09.020

    Article  CAS  PubMed  Google Scholar 

  44. Chen S, Tang C, Ding H, Wang Z, Liu X, Chai Y, Jiang W, Han Y, Zeng H (2020) Maf1 ameliorates sepsis-associated encephalopathy by suppressing the NF-kB/NLRP3 inflammasome signaling pathway. Front Immunol 11:594071. https://doi.org/10.3389/fimmu.2020.594071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen X, Liu G, Yuan Y, Wu G, Wang S, Yuan L (2019) NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-kappaB signaling. Cell Death Dis 10(12):906. https://doi.org/10.1038/s41419-019-2157-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Voet S, Srinivasan S, Lamkanfi M, van Loo G (2019) Inflammasomes in neuroinflammatory and neurodegenerative diseases. Embo Mol Med 11(6). https://doi.org/10.15252/emmm.201810248

  47. Yu W, Qin X, Zhang Y, Qiu P, Wang L, Zha W, Ren J (2020) Curcumin suppresses doxorubicin-induced cardiomyocyte pyroptosis via a PI3K/Akt/mTOR-dependent manner. Cardiovasc Diagn Ther 10(4):752–769. https://doi.org/10.21037/cdt-19-707

    Article  PubMed  PubMed Central  Google Scholar 

  48. Palma-Lara I, Martinez-Castillo M, Quintana-Perez JC, Arellano-Mendoza MG, Tamay-Cach F, Valenzuela-Limon OL, Garcia-Montalvo EA, Hernandez-Zavala A (2020) Arsenic exposure: a public health problem leading to several cancers. Regul Toxicol Pharmacol 110:104539. https://doi.org/10.1016/j.yrtph.2019.104539

    Article  CAS  PubMed  Google Scholar 

  49. Xiao J, Jiang X, Zhou Y, Sumayyah G, Zhou L, Tu B, Qin Q, Qiu J, Qin X, Zou Z, Chen C (2022) Results of a 30-day safety assessment in young mice orally exposed to polystyrene nanoparticles. Environ Pollut 292(Pt B):118184. https://doi.org/10.1016/j.envpol.2021.118184

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China

    Rao Gan, Haiyan Liu, Shaofeng Wu, Zhaoxin Tang & Lianmei Hu

  2. Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China

    Riming Huang

  3. Guangxi Nongken Yongxin Animal, Husbandry Group Co., Ltd, Nanning, 530022, Guangxi, China

    Ning Zhang

Authors
  1. Rao Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haiyan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shaofeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Riming Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhaoxin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ning Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lianmei Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: Rao Gan, Haiyan Liu; methodology: Gan Rao, Shaofeng Wu; formal analysis and investigation: Gan Rao, Ning Zhang, Riming Huang; writing—original draft preparation: Lianmei Hu; writing—review and editing: Lianmei Hu, Riming Huang; funding acquisition: Zhaoxin Tang, Lianmei Hu; resources: Lianmei Hu; supervision: Lianmei Hu.

Corresponding authors

Correspondence to Ning Zhang or Lianmei Hu.

Ethics declarations

Author Agreement

We the undersigned declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere.

We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed.

We further confirm that the order of authors listed in the manuscript has been approved by all of us. We understand that the Corresponding Author is the sole contact for the Editorial process. He/she is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs.

Signed by all the authors.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

• Oral intake of ATO-triggered hypothalamic toxicity in ducks.

• ATO cross BBB and lead to inflammation and pyroptosis in hypothalamic of ducks.

• Cur alleviated ATOinduced poising in hypothalamic of ducks.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 4223 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gan, R., Liu, H., Wu, S. et al. Curcumin Alleviates Arsenic Trioxide–Induced Inflammation and Pyroptosis via the NF-κB/NLRP3 Signaling Pathway in the Hypothalamus of Ducks. Biol Trace Elem Res 201, 2503–2511 (2023). https://doi.org/10.1007/s12011-022-03321-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03321-4

Keywords

Search

Navigation