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Pinocembrin pretreatment counteracts the chlorpyrifos-induced HO-1 downregulation, mitochondrial dysfunction, and inflammation in the SH-SY5Y cells

Abstract

Chlorpyrifos (CPF), an insecticide, induces pro-oxidant, pro-inflammatory, and pro-apoptotic effects in animal cells. Contamination with CPF occurs not only in farms, since CPF is found in the food consumed in homes. Recently, it was demonstrated that CPF affects the mitochondria, inhibiting components of the electron transfer chain (ETC), causing loss of mitochondrial membrane potential (MMP), and reducing the synthesis of adenosine triphosphate (ATP) by the Complex V. Pinocembrin (PB) is found in propolis and exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects in mammalian cells. PB is a potent inducer of the nuclear factor erythroid 2-related factor 2 (Nrf2), which is a major transcription factor controlling the expression of heme oxygease-1 (HO-1), among others. In the present work, we investigated whether PB would be able to prevent the mitochondrial and immune dysfunctions in the human neuroblastoma SH-SY5Y cells exposed to CPF. PB was tested at 1–25 µM for 4 h before the administration of CPF at 100 µM for additional 24 h. We found that PB prevented the CPF-induced inhibition of ETC, loss of MMP, and decline in the ATP synthesis. PB also promoted anti-inflammatory actions in this experimental model. Silencing of Nrf2 or inhibition of HO-1 suppressed the PB-induced effects in the CPF-challenged cells. Thus, PB promoted beneficial effects by a mechanism dependent on the Nrf2/HO-1/CO + BR axis in the CPF-treated cells.

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Data availability

All data generated or analysed during this study are included in this published article (and its supplementary information files).

References

  1. Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 1863:585–597. https://doi.org/10.1016/j.bbadis.2016.11.005

    CAS  Article  PubMed  Google Scholar 

  2. Alcaraz MJ, Fernández P, Guillén MI (2003) Anti-inflammatory actions of the heme oxygenase-1 pathway. Curr Pharm Des 9:2541–2551. https://doi.org/10.2174/1381612033453749

    CAS  Article  PubMed  Google Scholar 

  3. AlKahtane AA, Ghanem E, Bungau SG, Alarifi S, Ali D, AlBasher G, Alkahtani S, Aleya L, Abdel-Daim MM (2020) Carnosic acid alleviates chlorpyrifos-induced oxidative stress and inflammation in mice cerebral and ocular tissues. Environ Sci Pollut Res Int 27:11663–11670. https://doi.org/10.1007/s11356-020-07736-1

    CAS  Article  PubMed  Google Scholar 

  4. Araujo JA, Zhang M, Yin F (2012) Heme oxygenase-1, oxidation, inflammation, and atherosclerosis. Front Pharmacol 3:119. https://doi.org/10.3389/fphar.2012.00119

    Article  PubMed  PubMed Central  Google Scholar 

  5. Berne JP, Lauzier B, Rochette L, Vergely C (2012) Carbon monoxide protects against ischemia-reperfusion injury in vitro via antioxidant properties. Cell Physiol Biochem 29:475–484. https://doi.org/10.1159/000338501

    CAS  Article  PubMed  Google Scholar 

  6. Borriello M, Iannuzzi C, Sirangelo I (2019) Pinocembrin protects from AGE-induced cytotoxicity and inhibits non-enzymatic glycation in human insulin. Cells 8:385. https://doi.org/10.3390/cells8050385

    CAS  Article  PubMed Central  Google Scholar 

  7. Borutaite V, Morkuniene R, Brown GC (1999) Release of cytochrome c from heart mitochondria is induced by high Ca2+ and peroxynitrite and is responsible for Ca(2+)-induced inhibition of substrate oxidation. Biochim Biophys Acta 1453:41–48. https://doi.org/10.1016/s0925-4439(98)00082-9

    CAS  Article  PubMed  Google Scholar 

  8. Brasil FB, Bertolini Gobbo RC, Souza de Almeida FJ, Luckachaki MD, Dall’Oglio EL, de Oliveira MR (2021) The signaling pathway PI3K/Akt/Nrf2/HO-1 plays a role in the mitochondrial protection promoted by astaxanthin in the SH-SY5Y cells exposed to hydrogen peroxide. Neurochem Int. https://doi.org/10.1016/j.neuint.2021.105024

    Article  PubMed  Google Scholar 

  9. Breda CNS, Davanzo GG, Basso PJ, Saraiva Câmara NO, Moraes-Vieira PMM (2019) Mitochondria as central hub of the immune system. Redox Biol 26:101255. https://doi.org/10.1016/j.redox.2019.101255

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Catino S, Paciello F, Miceli F, Rolesi R, Troiani D, Calabrese V, Santangelo R, Mancuso C (2016) Ferulic acid regulates the Nrf2/Heme oxygenase-1 system and counteracts trimethyltin-induced neuronal damage in the human neuroblastoma cell line SH-SY5Y. Front Pharmacol 6:305. https://doi.org/10.3389/fphar.2015.00305

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Caughlan A, Newhouse K, Namgung U, Xia Z (2004) Chlorpyrifos induces apoptosis in rat cortical neurons that is regulated by a balance between p38 and ERK/JNK MAP kinases. Toxicol Sci 78:125–134. https://doi.org/10.1093/toxsci/kfh038

    CAS  Article  PubMed  Google Scholar 

  12. Choi S, Kim J, Kim JH, Lee DK, Park W, Park M, Kim S, Hwang JY, Won MH, Choi YK, Ryoo S, Ha KS, Kwon YG, Kim YM (2017) Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis. Exp Mol Med 49:e403. https://doi.org/10.1038/emm.2017.193

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Cuadrado A, Rojo AI (2008) Heme oxygenase-1 as a therapeutic target in neurodegenerative diseases and brain infections. Curr Pharm Des 14:429–442. https://doi.org/10.2174/138161208783597407

    CAS  Article  PubMed  Google Scholar 

  14. de Oliveira MR, Ferreira GC, Schuck PF, Dal Bosco SM (2015) Role for the PI3K/Akt/Nrf2 signaling pathway in the protective effects of carnosic acid against methylglyoxal-induced neurotoxicity in SH-SY5Y neuroblastoma cells. Chem Biol Interact 242:396–406. https://doi.org/10.1016/j.cbi.2015.11.003

    CAS  Article  PubMed  Google Scholar 

  15. de Oliveira MR, Peres A, Ferreira GC, Schuck PF, Bosco SM (2016a) Carnosic acid affords mitochondrial protection in chlorpyrifos-treated Sh-Sy5y cells. Neurotox Res 30:367–379. https://doi.org/10.1007/s12640-016-9620-x

    CAS  Article  PubMed  Google Scholar 

  16. de Oliveira MR, Nabavi SM, Braidy N, Setzer WN, Ahmed T, Nabavi SF (2016b) Quercetin and the mitochondria: a mechanistic view. Biotechnol Adv 34:532–549. https://doi.org/10.1016/j.biotechadv.2015.12.014

    CAS  Article  PubMed  Google Scholar 

  17. de Oliveira MR, Peres A, Ferreira GC (2017a) Pinocembrin attenuates mitochondrial dysfunction in human neuroblastoma SH-SY5Y cells exposed to methylglyoxal: role for the Erk1/2-Nrf2 signaling pathway. Neurochem Res 42:1057–1072. https://doi.org/10.1007/s11064-016-2140-5

    CAS  Article  PubMed  Google Scholar 

  18. de Oliveira MR, Peres A, Gama CS, Bosco SMD (2017b) Pinocembrin provides mitochondrial protection by the activation of the Erk1/2-Nrf2 signaling pathway in SH-SY5Y neuroblastoma cells exposed to paraquat. Mol Neurobiol 54:6018–6031. https://doi.org/10.1007/s12035-016-0135-5

    CAS  Article  PubMed  Google Scholar 

  19. de Oliveira MR, da Costa FG, Brasil FB, Peres A (2018) Pinocembrin suppresses H2O2-induced mitochondrial dysfunction by a mechanism dependent on the Nrf2/HO-1 axis in SH-SY5Y cells. Mol Neurobiol 55:989–1003. https://doi.org/10.1007/s12035-016-0380-7

    CAS  Article  PubMed  Google Scholar 

  20. Esteras N, Dinkova-Kostova AT, Abramov AY (2016) Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function. Biol Chem 397:383–400. https://doi.org/10.1515/hsz-2015-0295

    CAS  Article  PubMed  Google Scholar 

  21. Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–36. https://doi.org/10.1016/0009-8981(85)90135-4

    CAS  Article  PubMed  Google Scholar 

  22. Gomathy N, Sumantran VN, Shabna A, Sulochana KN (2015) Tolerance of ARPE 19 cells to organophosphorus pesticide chlorpyrifos is limited to concentration and time of exposure. Pestic Biochem Physiol 117:24–30. https://doi.org/10.1016/j.pestbp.2014.10.004

    CAS  Article  PubMed  Google Scholar 

  23. Green DR, Galluzzi L, Kroemer G (2014) Metabolic control of cell death. Science 345:1250256. https://doi.org/10.1126/science.1250256

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Gruber J, Fong S, Chen CB, Yoong S, Pastorin G, Schaffer S, Cheah I, Halliwell B (2013) Mitochondria-targeted antioxidants and metabolic modulators as pharmacological interventions to slow ageing. Biotechnol Adv 31:563–592. https://doi.org/10.1016/j.biotechadv.2012.09.005

    CAS  Article  PubMed  Google Scholar 

  25. Gu X, Zhang Q, Du Q, Shen H, Zhu Z (2017) Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice. Int Immunopharmacol 53:90–95. https://doi.org/10.1016/j.intimp.2017.10.005

    CAS  Article  PubMed  Google Scholar 

  26. Habtemariam S (2019) The Nrf2/HO-1 axis as targets for flavanones: neuroprotection by pinocembrin, naringenin, and eriodictyol. Oxid Med Cell Longev 2019:4724920. https://doi.org/10.1155/2019/4724920

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Hansen TW (2001) Bilirubin brain toxicity. J Perinatol. https://doi.org/10.1038/sj.jp.7210634

    Article  PubMed  Google Scholar 

  28. Harijith A, Ebenezer DL, Natarajan V (2014) Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol 5:352. https://doi.org/10.3389/fphys.2014.00352

    Article  PubMed  PubMed Central  Google Scholar 

  29. Holmström KM, Kostov RV, Dinkova-Kostova AT (2016) The multifaceted role of Nrf2 in mitochondrial function. Curr Opin Toxicol 1:80–91. https://doi.org/10.1016/j.cotox.2016.10.002

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hulsmans M, Holvoet P (2010) The vicious circle between oxidative stress and inflammation in atherosclerosis. J Cell Mol Med 14:70–78. https://doi.org/10.1111/j.1582-4934.2009.00978.x

    CAS  Article  PubMed  Google Scholar 

  31. Hwang YP, Kim HG, Han EH, Jeong HG (2008) Metallothionein-III protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a PI3K and ERK/Nrf2-dependent manner. Toxicol Appl Pharmacol 231:318–327. https://doi.org/10.1016/j.taap.2008.04.019

    CAS  Article  PubMed  Google Scholar 

  32. Jabaut J, Ather JL, Taracanova A, Poynter ME, Ckless K (2013) Mitochondria-targeted drugs enhance Nlrp3 inflammasome-dependent IL-1β secretion in association with alterations in cellular redox and energy status. Free Radic Biol Med 60:233–245. https://doi.org/10.1016/j.freeradbiomed.2013.01.025

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. Jansen T, Daiber A (2012) Direct antioxidant properties of bilirubin and biliverdin: Is there a role for biliverdin reductase? Front Pharmacol 3:30. https://doi.org/10.3389/fphar.2012.00030

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kirkby KA, Adin CA (2006) Products of heme oxygenase and their potential therapeutic applications. Am J Physiol Renal Physiol 290:F563–F571. https://doi.org/10.1152/ajprenal.00220.2005

    CAS  Article  PubMed  Google Scholar 

  35. Kishimoto Y, Kondo K, Momiyama Y (2019) The protective role of heme oxygenase-1 in atherosclerotic diseases. Int J Mol Sci 20:3628. https://doi.org/10.3390/ijms20153628

    CAS  Article  PubMed Central  Google Scholar 

  36. Kopjar N, Žunec S, Mendaš G, Micek V, Kašuba V, Mikolić A, Lovaković BT, Milić M, Pavičić I, Čermak AMM, Pizent A, Lucić Vrdoljak A, Želježić D (2018) Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats. Chem Biol Interact 279:51–63. https://doi.org/10.1016/j.cbi.2017.10.029

    CAS  Article  PubMed  Google Scholar 

  37. Kurek-Górecka A, Górecki M, Rzepecka-Stojko A, Balwierz R, Stojko J (2020) Bee products in dermatology and skin care. Molecules 25:556. https://doi.org/10.3390/molecules25030556

    CAS  Article  PubMed Central  Google Scholar 

  38. Lee JE, Park JH, Jang SJ, Koh HC (2014) Rosiglitazone inhibits chlorpyrifos-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells. Toxicol Appl Pharmacol 278:159–171. https://doi.org/10.1016/j.taap.2014.04.021

    CAS  Article  PubMed  Google Scholar 

  39. Li Q, Kobayashi M, Kawada T (2009) Chlorpyrifos induces apoptosis in human T cells. Toxicology 255:53–57. https://doi.org/10.1016/j.tox.2008.10.003

    CAS  Article  PubMed  Google Scholar 

  40. Li Y, Huang B, Ye T, Wang Y, Xia D, Qian J (2020) Physiological concentrations of bilirubin control inflammatory response by inhibiting NF-κB and inflammasome activation. Int Immunopharmacol 84:106520. https://doi.org/10.1016/j.intimp.2020.106520

    CAS  Article  PubMed  Google Scholar 

  41. Liu R, Wu CX, Zhou D, Yang F, Tian S, Zhang L, Zhang TT, Du GH (2012) Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE)-independent signaling pathways and regulating mitochondrion-mediated apoptosis. BMC Med 10:105. https://doi.org/10.1186/1741-7015-10-105

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Maines MD (1990) Multiple forms of biliverdin reductase: age-related change in pattern of expression in rat liver and brain. Mol Pharmacol 38:481–485

    CAS  PubMed  Google Scholar 

  43. Mathy-Hartert M, Deby-Dupont GP, Reginster JY, Ayache N, Pujol JP, Henrotin YE (2002) Regulation by reactive oxygen species of interleukin-1beta, nitric oxide and prostaglandin E(2) production by human chondrocytes. Osteoarthritis Cartilage 10:547–555. https://doi.org/10.1053/joca.2002.0789

    CAS  Article  PubMed  Google Scholar 

  44. Mhillaj E, Papi M, Paciello F, Silvestrini A, Rolesi R, Palmieri V, Perini G, Fetoni AR, Trabace L, Mancuso C (2020) Celecoxib exerts neuroprotective effects in β-amyloid-treated SH-SY5Y cells through the regulation of heme oxygenase-1: novel insights for an old drug. Front Cell Dev Biol 8:561179. https://doi.org/10.3389/fcell.2020.561179

    Article  PubMed  PubMed Central  Google Scholar 

  45. Narra MR, Rajender K, Reddy RR, Murty US, Begum G (2017) Insecticides induced stress response and recuperation in fish: biomarkers in blood and tissues related to oxidative damage. Chemosphere 168:350–357. https://doi.org/10.1016/j.chemosphere.2016.10.066

    CAS  Article  PubMed  Google Scholar 

  46. Niranjan R (2014) The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson’s disease: focus on astrocytes. Mol Neurobiol 49(1):28–38. https://doi.org/10.1007/s12035-013-8483-x

    CAS  Article  PubMed  Google Scholar 

  47. Ostrow JD, Pascolo L, Brites D, Tiribelli C (2004) Molecular basis of bilirubin-induced neurotoxicity. Trends Mol Med 10:65–70. https://doi.org/10.1016/j.molmed.2003.12.003

    CAS  Article  PubMed  Google Scholar 

  48. Otterbein LE, Bach FH, Alam J, Soares M, Tao LuH, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. https://doi.org/10.1038/74680

    Article  PubMed  Google Scholar 

  49. Parfenova H, Leffler CW, Basuroy S, Liu J, Fedinec AL (2012) Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. J Cereb Blood Flow Metab 32:1024–1034. https://doi.org/10.1038/jcbfm.2012.13

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. Patergnani S, Bouhamida E, Leo S, Pinton P, Rimessi A (2021) Mitochondrial oxidative stress and “mito-inflammation”: actors in the diseases. Biomedicines 9:216. https://doi.org/10.3390/biomedicines9020216

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. Poderoso JJ, Carreras MC, Lisdero C, Riobó N, Schöpfer F, Boveris A (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328:85–92. https://doi.org/10.1006/abbi.1996.0146

    CAS  Article  PubMed  Google Scholar 

  52. Richardson RJ (1995) Assessment of the neurotoxic potential of chlorpyrifos relative to other organophosphorus compounds: a critical review of the literature. J Toxicol Environ Health 44:135–165. https://doi.org/10.1080/15287399509531952

    CAS  Article  PubMed  Google Scholar 

  53. Rieske JS (1967) The quantitative determination of mitochondrial hemoproteins. Methods Enzymol 10:488–493

    CAS  Article  Google Scholar 

  54. Rimessi A, Previati M, Nigro F, Wieckowski MR, Pinton P (2016) Mitochondrial reactive oxygen species and inflammation: molecular mechanisms, diseases and promising therapies. Int J Biochem Cell Biol 81:281–293. https://doi.org/10.1016/j.biocel.2016.06.015

    CAS  Article  PubMed  Google Scholar 

  55. Rodrigues CM, Solá S, Brites D (2002) Bilirubin induces apoptosis via the mitochondrial pathway in developing rat brain neurons. Hepatology 35:1186–1195. https://doi.org/10.1053/jhep.2002.32967

    CAS  Article  PubMed  Google Scholar 

  56. Saha S, Buttari B, Panieri E, Profumo E, Saso L (2020) An overview of Nrf2 signaling pathway and its role in inflammation. Molecules 25:5474. https://doi.org/10.3390/molecules25225474

    CAS  Article  PubMed Central  Google Scholar 

  57. Samarghandian S, Foadoddin M, Zardast M, Mehrpour O, Sadighara P, Roshanravan B, Farkhondeh T (2020) The impact of age-related sub-chronic exposure to chlorpyrifos on metabolic indexes in male rats. Environ Sci Pollut Res Int 27:22390–22399. https://doi.org/10.1007/s11356-020-08814-0

    CAS  Article  PubMed  Google Scholar 

  58. Sarkar B, Dhiman M, Mittal S, Mantha AK (2017) Curcumin revitalizes Amyloid beta (25–35)-induced and organophosphate pesticides pestered neurotoxicity in SH-SY5Y and IMR-32 cells via activation of APE1 and Nrf2. Metab Brain Dis 32:2045–2061. https://doi.org/10.1007/s11011-017-0093-2

    CAS  Article  PubMed  Google Scholar 

  59. Schapira AH, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD (1990) Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem 55:2142–2145. https://doi.org/10.1111/j.1471-4159.1990.tb05809.x

    CAS  Article  PubMed  Google Scholar 

  60. Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KR, Snyder SH (2009) Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proc Natl Acad Sci U S A 106:5171–5176. https://doi.org/10.1073/pnas.0813132106

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sepand MR, Aliomrani M, Hasani-Nourian Y, Khalhori MR, Farzaei MH, Sanadgol N (2020) Mechanisms and pathogenesis underlying environmental chemical-induced necroptosis. Environ Sci Pollut Res Int 27:37488–37501. https://doi.org/10.1007/s11356-020-09360-5

    CAS  Article  PubMed  Google Scholar 

  62. Singh N, Lawana V, Luo J, Phong P, Abdalla A, Palanisamy B, Rokad D, Sarkar S, Jin H, Anantharam V, Kanthasamy AG, Kanthasamy A (2018) Organophosphate pesticide chlorpyrifos impairs STAT1 signaling to induce dopaminergic neurotoxicity: Implications for mitochondria mediated oxidative stress signaling events. Neurobiol Dis 117:82–113. https://doi.org/10.1016/j.nbd.2018.05.019

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. Suski JM, Lebiedzinska M, Bonora M, Pinton P, Duszynski J, Wieckowski MR (2012) Relation between mitochondrial membrane potential and ROS formation. Methods Mol Biol 810:183–205. https://doi.org/10.1007/978-1-61779-382-0_12

    CAS  Article  PubMed  Google Scholar 

  64. Tassi S, Carta S, Vené R, Delfino L, Ciriolo MR, Rubartelli A (2009) Pathogen-induced interleukin-1beta processing and secretion is regulated by a biphasic redox response. J Immunol 183:1456–1462. https://doi.org/10.4049/jimmunol.0900578

    CAS  Article  PubMed  Google Scholar 

  65. Ubaid Ur Rahman H, Asghar W, Nazir W, Sandhu MA, Ahmed A, Khalid N (2021) A comprehensive review on chlorpyrifos toxicity with special reference to endocrine disruption: Evidence of mechanisms, exposures and mitigation strategies. Sci Total Environ 755:142649. https://doi.org/10.1016/j.scitotenv.2020.142649

    CAS  Article  PubMed  Google Scholar 

  66. Wakabayashi N, Slocum SL, Skoko JJ, Shin S, Kensler TW (2010) When NRF2 talks, who’s listening? Antioxid Redox Signal 13:1649–1663. https://doi.org/10.1089/ars.2010.3216

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. Wang Y, Gao J, Miao Y, Cui Q, Zhao W, Zhang J, Wang H (2014) Pinocembrin protects SH-SY5Y cells against MPP+-induced neurotoxicity through the mitochondrial apoptotic pathway. J Mol Neurosci 53:537–545. https://doi.org/10.1007/s12031-013-0219-x

    CAS  Article  PubMed  Google Scholar 

  68. Wang H, Wang Y, Zhao L, Cui Q, Wang Y, Du G (2016a) Pinocembrin attenuates MPP(+)-induced neurotoxicity by the induction of heme oxygenase-1 through ERK1/2 pathway. Neurosci Lett 612:104–109. https://doi.org/10.1016/j.neulet.2015.11.048

    CAS  Article  PubMed  Google Scholar 

  69. Wang Y, Miao Y, Mir AZ, Cheng L, Wang L, Zhao L, Cui Q, Zhao W, Wang H (2016b) Inhibition of beta-amyloid-induced neurotoxicity by pinocembrin through Nrf2/HO-1 pathway in SH-SY5Y cells. J Neurol Sci 368:223–230. https://doi.org/10.1016/j.jns.2016.07.010

    CAS  Article  PubMed  Google Scholar 

  70. Waza AA, Hamid Z, Ali S, Bhat SA, Bhat MA (2018) A review on heme oxygenase-1 induction: is it a necessary evil. Inflamm Res 67:579–588. https://doi.org/10.1007/s00011-018-1151-x

    CAS  Article  PubMed  Google Scholar 

  71. Weinberg SE, Sena LA, Chandel NS (2015) Mitochondria in the regulation of innate and adaptive immunity. Immunity 42:406–417. https://doi.org/10.1016/j.immuni.2015.02.002

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. Yang D, Elner SG, Bian ZM, Till GO, Petty HR, Elner VM (2007) Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells. Exp Eye Res 85:462–472. https://doi.org/10.1016/j.exer.2007.06.013

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  73. Yu F, Wang Z, Ju B, Wang Y, Wang J, Bai D (2008) Apoptotic effect of organophosphorus insecticide chlorpyrifos on mouse retina in vivo via oxidative stress and protection of combination of vitamins C and E. Exp Toxicol Pathol 59:415–423. https://doi.org/10.1016/j.etp.2007.11.007

    CAS  Article  PubMed  Google Scholar 

  74. Zhang Y, Jia Q, Hu C, Han M, Guo Q, Li S, Bo C, Zhang Y, Qi X, Sai L, Peng C (2021) Effects of chlorpyrifos exposure on liver inflammation and intestinal flora structure in mice. Toxicol Res (camb) 10:141–149. https://doi.org/10.1093/toxres/tfaa108

    CAS  Article  Google Scholar 

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Funding

MRO receives a “Bolsa de Produtividade em Pesquisa 2—PQ2” fellow from the Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (protocol number 301273/2018-9). This work received financial support from CNPq (protocol numbers 400216/2016-7).

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Conceptualization: MRO; Methodology: FBB, FJSA, MDL, ELD, MRO; Formal analysis and investigation: FBB, FJSA, MDL, MRO; Writing—original draft preparation: MRO; Writing—review and editing: FBB, FJS A, MDL, ELD, MRO; Funding acquisition: FBB, MRO, and ELD; Resources: FBB, MRO, and ELD; Supervision: MRO.

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Correspondence to Marcos Roberto de Oliveira.

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Brasil, F.B., de Almeida, F.J.S., Luckachaki, M.D. et al. Pinocembrin pretreatment counteracts the chlorpyrifos-induced HO-1 downregulation, mitochondrial dysfunction, and inflammation in the SH-SY5Y cells. Metab Brain Dis (2021). https://doi.org/10.1007/s11011-021-00803-7

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Keywords

  • Pinocembrin
  • Chlorpyrifos
  • Mitochondria
  • Redox signaling
  • Nrf2
  • HO-1