The Antioxidant Activity of Betanin protects MRC-5 cells Against Cadmium Induced Toxicity.
Apoptosis
Betanin
Cadmium
Cytotoxicity
Reactive oxygen species
Journal
Biological trace element research
ISSN: 1559-0720
Titre abrégé: Biol Trace Elem Res
Pays: United States
ID NLM: 7911509
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
04
02
2023
accepted:
05
04
2023
medline:
20
9
2023
pubmed:
26
4
2023
entrez:
26
4
2023
Statut:
ppublish
Résumé
Cadmium (Cd) can induce both acute and chronic effects in the lungs depending on the time and the exposure route. Betanin is a component derived from the roots of red beets and it is well-known for its antioxidant and anti-apoptosis effects. The current study aimed to survey the protective effects of betanin on cell toxicity induced by Cd. Different concentration of Cd alone and in combination with betanin was assessed in MRC-5 cells. The viability and oxidative stress were measured using resazurin and DCF-DA methods respectively. Apoptotic cells were assessed by PI staining of the fragmented DNA and western blot analysis detected the activation of caspase 3 and PARP proteins. Cd exposure for 24 h declined viability and increased ROS production in MRC-5 cells compared to the control group (p < 0.001). Also, Cd (35 μM) elevated DNA fragmentation (p < 0.05), and the level of caspase 3-cleaved and cleaved PARP proteins in MRC-5 cells (p < 0.001). Co-treatment of cells with betanin for 24 h significantly enhanced viability in concentrations of 1.25 and 2.5 μM (p < 0.001) and 5 μM (p < 0.05) and declined ROS generation (1.25 and 5 μM p < 0.001, and 2.5 μM p < 0.01). As well as, betanin reduced DNA fragmentation (p < 0.01), and the markers of apoptosis (p < 0.001) compared to the Cd-treated group. In conclusion, betanin protects lung cells against Cd-induced toxicity through antioxidant activity and inhibition of apoptosis.
Identifiants
pubmed: 37099220
doi: 10.1007/s12011-023-03662-8
pii: 10.1007/s12011-023-03662-8
doi:
Substances chimiques
Antioxidants
0
Cadmium
00BH33GNGH
Reactive Oxygen Species
0
Caspase 3
EC 3.4.22.-
betanin
5YJC992ZP6
Betacyanins
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5183-5191Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Matović V, Buha A, Ðukić-Ćosić D, Bulat Z (2015) Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol 78:130–140
doi: 10.1016/j.fct.2015.02.011
Najeeb U, Jilani G, Ali S, Sarwar M, Xu L, Zhou W (2011) Insights into cadmium induced physiological and ultra-structural disorders in Juncus effusus L. and its remediation through exogenous citric acid. J Hazard Mater 186:565–574
doi: 10.1016/j.jhazmat.2010.11.037
Shayan M, Mehri S, Razavi BM, Hosseinzadeh H (2023) Minocycline protects PC12 cells against cadmium-induced neurotoxicity by modulating apoptosis. Biol Trace Elem Res 201:1946–1954
doi: 10.1007/s12011-022-03305-4
Soria J, Gauthier D, Falcoz Q, Flamant G, Mazza G (2013) Local CFD kinetic model of cadmium vaporization during fluid bed incineration of municipal solid waste. J Hazard Mater 248–249:276–284
doi: 10.1016/j.jhazmat.2013.01.015
Luevano J, Damodaran C (2014) A review of molecular events of cadmium-induced carcinogenesis. J Environ Pathol Toxicol Oncol 33:183–194
pmcid: 4183964
doi: 10.1615/JEnvironPatholToxicolOncol.2014011075
Samarawickrama GJbMW, Elsevier/North Holland, Amsterdam (1979) The chemistry, biochemistry and biology of cadmium 370–373, North Holland, Amsterdam
Odewumi CO, Latinwo LM, Ruden ML, Badisa VL, Fils-Aime S, Badisa RB (2016) Modulation of cytokines and chemokines expression by NAC in cadmium chloride treated human lung cells. Environ Toxicol 31:1612–1619
doi: 10.1002/tox.22165
Habeebu SS, Liu J, Klaassen CD (1998) Cadmium-induced apoptosis in mouse liver. Toxicol Appl Pharmacol 149:203–209
doi: 10.1006/taap.1997.8334
Ganguly K, Levänen B, Palmberg L, Åkesson A, Lindén A (2018) Cadmium in tobacco smokers: a neglected link to lung disease? Eur Respir Rev 27:1–8
Lee BK, Kim Y (2012) Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: analysis of 2008–2009 Korean National Health and Nutrition Examination Survey data. Environ Res 112:155–163
doi: 10.1016/j.envres.2011.10.013
Yang CF, Shen HM, Shen Y, Zhuang ZX, Ong CN (1997) Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells). Environ Health Perspect 105:712–716
pmcid: 1470098
doi: 10.1289/ehp.97105712
Park JH, Lee BM, Kim HS (2021) Potential protective roles of curcumin against cadmium-induced toxicity and oxidative stress. J Toxicol Environ Health B Crit Rev 24:95–118
doi: 10.1080/10937404.2020.1860842
Karoui-Kharrat D, Kaddour H, Hamdi Y, Mokni M, Amri M, Mezghani S (2017) Response of antioxidant enzymes to cadmium-induced cytotoxicity in rat cerebellar granule neurons. Open Life Sci 12:113–119
doi: 10.1515/biol-2017-0013
Kitamura M, Hiramatsu N (2010) The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity. Biometals 23:941–950
doi: 10.1007/s10534-010-9296-2
Matović V, Buha A, Bulat Z, Dukić-Ćosić D (2011) Cadmium toxicity revisited: focus on oxidative stress induction and interactions with zinc and magnesium. Arh Hig Rada Toksikol 62:65–76
doi: 10.2478/10004-1254-62-2011-2075
Sarkar A, Ravindran G, Krishnamurthy V (2013) A brief review on the effect of cadmium toxicity: from cellular to organ level. Int J Biotechnol Res 3:17–36
Coutant A, Lebeau J, Bidon-Wagner N, Levalois C, Lectard B, Chevillard S (2006) Cadmium-induced apoptosis in lymphoblastoid cell line: involvement of caspase-dependent and -independent pathways. Biochimie 88:1815–1822
doi: 10.1016/j.biochi.2006.09.018
Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A (2020) The Effects of Cadmium Toxicity. Int J Environ Res Public Health 17:1–24
Bhattacharya S (2018) The role of medicinal plants and natural products in melioration of cadmium toxicity. Orient Pharm Exp Med 18:177–186
doi: 10.1007/s13596-018-0323-0
Vulić J, Čanadanović-Brunet J, Ćetković G, Tumbas V, Djilas S, Četojević-Simin D, Čanadanović V (2012) Antioxidant and cell growth activities of beet root pomace extracts. J Funct Foods 4:670–678
doi: 10.1016/j.jff.2012.04.008
Dhananjayan I, Kathiroli S, Subramani S, Veerasamy V (2017) Ameliorating effect of betanin, a natural chromoalkaloid by modulating hepatic carbohydrate metabolic enzyme activities and glycogen content in streptozotocin - nicotinamide induced experimental rats. Biomed Pharmacother 88:1069–1079
doi: 10.1016/j.biopha.2017.01.146
Hadipour E, Fereidoni M, Tayarani-Najaran Z (2020) Betanin attenuates oxidative stress induced by 6-OHDA in PC12 cells via SAPK/JNK and PI3 K pathways. Neurochem Res 45:395–403
doi: 10.1007/s11064-019-02927-w
Kanner J, Harel S, Granit R (2001) Betalains–a new class of dietary cationized antioxidants. J Agric Food Chem 49:5178–5185
doi: 10.1021/jf010456f
Tesoriere L, Butera D, Allegra M, Fazzari M, Livrea MA (2005) Distribution of betalain pigments in red blood cells after consumption of cactus pear fruits and increased resistance of the cells to ex vivo induced oxidative hemolysis in humans. J Agric Food Chem 53:1266–1270
doi: 10.1021/jf048134+
Dominguez H, Muñoz MJG (2017) Water extraction of bioactive compounds: from plants to drug development. Elsevier Vigo, Spain
Dörnenburg H, Knorr D (1996) Generation of colors and flavors in plant cell and tissue cultures. Crit Rev Plant Sci 15:141–168
doi: 10.1080/07352689.1996.10393184
Georgiev VG, Weber J, Kneschke EM, Denev PN, Bley T, Pavlov AI (2010) Antioxidant activity and phenolic content of betalain extracts from intact plants and hairy root cultures of the red beetroot Beta vulgaris cv. Detroit dark red. Plant Foods Hum Nutr 65:105–111
doi: 10.1007/s11130-010-0156-6
Gliszczyńska-Swigło A, Szymusiak H, Malinowska P (2006) Betanin, the main pigment of red beet: molecular origin of its exceptionally high free radical-scavenging activity. Food Addit Contam 23:1079–1087
doi: 10.1080/02652030600986032
Alqasmi I (2023) Ameliorative potential of betanin on cigarette smoke extract-induced respiratory mucosal inflammation and oxidative stress in the adult zebrafish model. Pharmacogn Mag :09731296221145075, 0:1–10
Butera D, Tesoriere L, Di Gaudio F, Bongiorno A, Allegra M, Pintaudi AM, Kohen R, Livrea MA (2002) Antioxidant activities of sicilian prickly pear (Opuntia ficus indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin. J Agric Food Chem 50:6895–6901
doi: 10.1021/jf025696p
Esatbeyoglu T, Wagner AE, Motafakkerazad R, Nakajima Y, Matsugo S, Rimbach G (2014) Free radical scavenging and antioxidant activity of betanin: electron spin resonance spectroscopy studies and studies in cultured cells. Food Chem Toxicol 73:119–126
doi: 10.1016/j.fct.2014.08.007
Clifford T, Constantinou CM, Keane KM, West DJ, Howatson G, Stevenson EJ (2017) The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans. Eur J Nutr 56:1245–1254
doi: 10.1007/s00394-016-1173-5
Zhang Q, Pan J, Wang Y, Lubet R, You M (2013) Beetroot red (betanin) inhibits vinyl carbamate- and benzo(a)pyrene-induced lung tumorigenesis through apoptosis. Mol Carcinog 52:686–691
doi: 10.1002/mc.21907
Song F, Zuo X, Zhao Y, Li Q, Tian Z, Yang Y (2019) Betanin-enriched red beet extract attenuated platelet activation and aggregation by suppressing Akt and P38 Mitogen-activated protein kinases phosphorylation. J Funct Foods 61:103491
doi: 10.1016/j.jff.2019.103491
Tan D, Wang Y, Bai B, Yang X, Han J (2015) Betanin attenuates oxidative stress and inflammatory reaction in kidney of paraquat-treated rat. Food Chem Toxicol 78:141–146
doi: 10.1016/j.fct.2015.01.018
Tural K, Ozden O, Bilgi Z, Kubat E, Ermutlu CS, Merhan O, Tasoglu I (2021) The protective effect of betanin and copper on spinal cord ischemia–reperfusion injury. J Spinal Cord Med : 1–7, 44:704–710
Fu Y, Shi J, Xie S-Y, Zhang T-Y, Soladoye OP, Aluko RE (2020) Red Beetroot Betalains: Perspectives on Extraction, Processing, and Potential Health Benefits. J Agric Food Chem 68:11595–11611
doi: 10.1021/acs.jafc.0c04241
Han J, Ma D, Zhang M, Yang X, Tan D (2015) Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia. BioMed Res Int 2015:1–9
Han J, Zhang Z, Yang S, Wang J, Yang X, Tan D (2014) Betanin attenuates paraquat-induced liver toxicity through a mitochondrial pathway. Food Chem Toxicol 70:100–106
doi: 10.1016/j.fct.2014.04.038
Zielińska-Przyjemska M, Olejnik A, Kostrzewa A, Łuczak M, Jagodziński PP, Baer-Dubowska W (2012) The beetroot component betanin modulates ROS production, DNA damage and apoptosis in human polymorphonuclear neutrophils. Phytother Res 26:845–852
doi: 10.1002/ptr.3649
Mukhtar-Fayyad D (2011) Cytocompatibility of new bioceramic-based materials on human fibroblast cells (MRC-5). Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112:e137-142
doi: 10.1016/j.tripleo.2011.05.042
Wang J, Li JZ, Lu AX, Zhang KF, Li BJ (2014) Anticancer effect of salidroside on A549 lung cancer cells through inhibition of oxidative stress and phospho-p38 expression. Oncol Lett 7:1159–1164
pmcid: 3961258
doi: 10.3892/ol.2014.1863
Vancsik T, Forika G, Balogh A, Kiss E, Krenacs T (2019) Modulated electro-hyperthermia induced p53 driven apoptosis and cell cycle arrest additively support doxorubicin chemotherapy of colorectal cancer in vitro. Cancer Med 8:4292–4303
pmcid: 6675742
doi: 10.1002/cam4.2330
Gaubin Y, Vaissade F, Croute F, Beau B, Soleilhavoup J, Murat J (2000) Implication of free radicals and glutathione in the mechanism of cadmium-induced expression of stress proteins in the A549 human lung cell-line. Biochim Biophys Acta 1495:4–13
doi: 10.1016/S0167-4889(99)00149-4
Odewumi CO, Badisa VL, Le UT, Latinwo LM, Ikediobi CO, Badisa RB, Darling-Reed SF (2011) Protective effects of N-acetylcysteine against cadmium-induced damage in cultured rat normal liver cells. Int J Mol Med 27:243–248
doi: 10.3892/ijmm.2010.564
Wang J, Zhu H, Liu X, Liu Z (2014) N-acetylcysteine protects against cadmium-induced oxidative stress in rat hepatocytes. J Vet Sci 15:485–493
pmcid: 4269590
doi: 10.4142/jvs.2014.15.4.485
Chairuangkitti P, Lawanprasert S, Roytrakul S, Aueviriyavit S, Phummiratch D, Kulthong K, Chanvorachote P, Maniratanachote R (2013) Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways. Toxicol In Vitro 27:330–338
doi: 10.1016/j.tiv.2012.08.021
Ramazani E, Fereidoni M, Tayarani-Najaran Z (2019) Protective effects of vitamin K2 on 6-OHDA-induced apoptosis in PC12 cells through modulation bax and caspase-3 activation. Mol Biol Rep 46:5777–5783
doi: 10.1007/s11033-019-05011-2
Riccardi C, Nicoletti I (2006) Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc 1:1458–1461
doi: 10.1038/nprot.2006.238
Shih CM, Wu JS, Ko WC, Wang LF, Wei YH, Liang HF, Chen YC, Chen CT (2003) Mitochondria-mediated caspase-independent apoptosis induced by cadmium in normal human lung cells. J Cell Biochem 89:335–347
doi: 10.1002/jcb.10488
Yu J, Sun R, Zhao Z, Wang Y (2014) Auricularia polytricha polysaccharides induce cell cycle arrest and apoptosis in human lung cancer A549 cells. Int J Biol Macromol 68:67–71
doi: 10.1016/j.ijbiomac.2014.04.018
Kianfar M, Nezami A, Mehri S, Hosseinzadeh H, Hayes AW, Karimi G (2020) The protective effect of fasudil against acrylamide-induced cytotoxicity in PC12 cells. Drug Chem Toxicol 43:595–601
doi: 10.1080/01480545.2018.1536140
Låg M, Rodionov D, Ovrevik J, Bakke O, Schwarze PE, Refsnes M (2010) Cadmium-induced inflammatory responses in cells relevant for lung toxicity: Expression and release of cytokines in fibroblasts, epithelial cells and macrophages. Toxicol Lett 193:252–260
doi: 10.1016/j.toxlet.2010.01.015
Unsal V, Dalkıran T, Çiçek M, Kölükçü E (2020) The role of natural antioxidants against reactive oxygen species produced by cadmium toxicity: a review. Adv Pharm Bull 10:184–202
pmcid: 7191230
doi: 10.34172/apb.2020.023
Liu J, Qu W, Kadiiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 238:209–214
pmcid: 4287357
doi: 10.1016/j.taap.2009.01.029
Knoell DL, Wyatt TA (2021) The adverse impact of cadmium on immune function and lung host defense. Semin Cell Dev Biol 115:70–76
doi: 10.1016/j.semcdb.2020.10.007
Person RJ, Tokar EJ, Xu Y, Orihuela R, Ngalame NN, Waalkes MP (2013) Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells. Toxicol Appl Pharmacol 273:281–288
doi: 10.1016/j.taap.2013.06.013
Kiran Kumar K, Naveen Kumar M, Patil RH, Nagesh R, Hegde SM, Kavya K, Babu R, Ramesh GT, Sharma SC (2016) Cadmium induces oxidative stress and apoptosis in lung epithelial cells. Toxicol Mech Methods 26:658–666
doi: 10.1080/15376516.2016.1223240
Odewumi C, Latinwo LM, Sinclair A, Badisa VL, Abdullah A, Badisa RB (2015) Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells. Mol Med Rep 12:6422–6426
pmcid: 4626121
doi: 10.3892/mmr.2015.4316
Son Y-O, Wang L, Poyil P, Budhraja A, Hitron JA, Zhang Z, Lee J-C, Shi X (2012) Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling. Toxicol Appl Pharmacol 264:153–160
pmcid: 3462234
doi: 10.1016/j.taap.2012.07.028
Wang S, Ren X, Hu X, Zhou L, Zhang C, Zhang M (2019) Cadmium-induced apoptosis through reactive oxygen species-mediated mitochondrial oxidative stress and the JNK signaling pathway in TM3 cells, a model of mouse Leydig cells. Toxicol Appl Pharmacol 368:37–48
doi: 10.1016/j.taap.2019.02.012
Wätjen W, Beyersmann D (2004) Cadmium-induced apoptosis in C6 glioma cells: influence of oxidative stress. Biometals 17:65–78
doi: 10.1023/A:1024405119018
Yin L, Dai Y, Cui Z, Jiang X, Liu W, Han F, Lin A, Cao J, Liu J (2017) The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity. Toxicol Appl Pharmacol 314:98–108
doi: 10.1016/j.taap.2016.11.013
Kundu S, Sengupta S, Bhattacharyya A (2011) EGFR upregulates inflammatory and proliferative responses in human lung adenocarcinoma cell line (A549), induced by lower dose of cadmium chloride. Inhal Toxicol 23:339–348
doi: 10.3109/08958378.2011.572931
Esatbeyoglu T, Wagner AE, Schini-Kerth VB, Rimbach G (2015) Betanin—A food colorant with biological activity. Mol Nutr Food Res 59:36–47
doi: 10.1002/mnfr.201400484
Lee C-Y, Su C-H, Tsai P-K, Yang M-L, Ho Y-C, Lee S-S, Chen C-H, Chen W-Y, Lin M-L, Chen C-J (2018) Cadmium nitrate-induced neuronal apoptosis is protected by N-acetyl-l-cysteine via reducing reactive oxygen species generation and mitochondria dysfunction. Biomed Pharmacother 108:448–456
doi: 10.1016/j.biopha.2018.09.054
Oh S-H, Lim S-C (2006) A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicol Appl Pharmacol 212:212–223
doi: 10.1016/j.taap.2005.07.018
Shih CM, Ko WC, Wu JS, Wei YH, Wang LF, Chang EE, Lo TY, Cheng HH, Chen CT (2004) Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. J Cell Biochem 91:384–397
doi: 10.1002/jcb.10761
Zhou Y-j, Zhang S-p, Liu C-w, Cai Y-q (2009) The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK1 cells. Toxicol In Vitro 23:288–294
doi: 10.1016/j.tiv.2008.12.009
Kwon KY, Jang JH, Choi WI, Ramachandran S, Cho CH, Cagle PT (2006) Expression of apoptotic nuclei by ultrastructural terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling and detection of FasL, caspases and PARP protein molecules in cadmium induced acute alveolar cell injury. Toxicology 218:197–204
doi: 10.1016/j.tox.2005.10.013
Balachandran C, Sangeetha B, Duraipandiyan V, Raj MK, Ignacimuthu S, Al-Dhabi N, Balakrishna K, Parthasarathy K, Arulmozhi N, Arasu MV (2014) A flavonoid isolated from Streptomyces sp. (ERINLG-4) induces apoptosis in human lung cancer A549 cells through p53 and cytochrome c release caspase dependant pathway. Chem Biol Interact 224:24–35
doi: 10.1016/j.cbi.2014.09.019
Xu P, Cai X, Zhang W, Li Y, Qiu P, Lu D, He X (2016) Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2 (Ca 2+)/Caspase-3/PARP-1 pathway. Apoptosis 21:1125–1143
doi: 10.1007/s10495-016-1270-1
Pascal JM (2018) The comings and goings of PARP-1 in response to DNA damage. DNA Repair 71:177–182
pmcid: 6637744
doi: 10.1016/j.dnarep.2018.08.022
Kim J, Soh J (2009) Cadmium-induced apoptosis is mediated by the translocation of AIF to the nucleus in rat testes. Toxicol Lett 188:45–51
doi: 10.1016/j.toxlet.2009.03.006
Spalm FHP, Vera MS, Dibo MJ, Simón MV, Politi LE, Rotstein NP (2019) Ceramide induces the death of retina photoreceptors through activation of parthanatos. Mol Neurobiol 56:4760–4777
doi: 10.1007/s12035-018-1402-4
Ou L, Wang H, Wu Z, Wang P, Yang L, Li X, Sun K, Zhu X, Zhang R (2021) Effects of cadmium on osteoblast cell line: Exportin 1 accumulation, p-JNK activation, DNA damage and cell apoptosis. Ecotoxicol Environ Saf 208:111668
doi: 10.1016/j.ecoenv.2020.111668
Oral B, Guney M, Demirin H, Ozguner M, Giray SG, Take G, Mungan T, Altuntas I (2006) Endometrial damage and apoptosis in rats induced by dichlorvos and ameliorating effect of antioxidant vitamins E and C. Reprod Toxicol 22:783–790
doi: 10.1016/j.reprotox.2006.08.003