Volume 26, Issue 1 (March 2022)                   Physiol Pharmacol 2022, 26(1): 88-100 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Abnosi M H, Aliyari Babolghani Z. Diethylhexyl phthalate induced oxidative stress and caused metabolic imbalance in bone marrow mesenchymal stem cells. Physiol Pharmacol 2022; 26 (1) :88-100
URL: http://ppj.phypha.ir/article-1-1716-en.html
Abstract:   (1489 Views)
Introduction: Diethylhexyl phthalate (DEHP) is leaching form polyvinyl chloride to cause animal toxicity. In our previous study, DEHP caused osteoblasts mortality in vitro, since rat bone marrow mesenchymal stem cells (MSCs) is the cellular back up for osteoblasts; therefore its effect on MSCs was investigated. Methods: MSCs were extracted from Westar rats and treated with 0.5 to 2500μM of DEHP for 12, 24 and 48h to study the viability. Then further investigations, including proliferation, cell morphology, sodium and potassium level, concentration of calcium, total protein, activity of metabolic enzymes (ALT, AST, ALP, LDH), malondialdehyde (MDA) level, total antioxidant capacity, activity of superoxide dismutase (SOD) and catalase (CAT) were measured using selected concentration (100, 500 and 1500μM). Results: The 100μM of DEHP did not change the viability and biochemical factor after 48h but colony forming assay and population doubling number was significantly affected. Th 500μM only reduced the viability at 24 and 48h, while 1500μM caused the significant reduction at all the periods. These two concentrations, caused significant proliferation reduction as well as significant increase in calcium and sodium level, LDH activity and MDA level. In addition, we observed decrease in potassium, total protein, activity of metabolic enzymes and activity of CAT and SOD significantly. Conclusion: DEHP has reduced viability and proliferation of MSCs through metabolic change, alteration in cellular ultrastructure, ionic imbalance and induction of oxidative stress.
Full-Text [PDF 1023 kb]   (560 Downloads)    

1. Abnosi MH, Aliyari Babolghani Z. The Inhibitory Role of Di-2-ethylhexyl phthalate on osteogenic differentiation of mesenchymal stem cells via down-regulation of runx2 and membrane function impairment. Int J Med Toxicol Forensic Med 2020; 10: 26673. [DOI:10.32598/ijmtfm.v10i2.26673]
2. Abnosi MH, Yari S. The toxic effect of gallic acid on biochemical factors, viability and proliferation of rat bone marrow mesenchymal stem cells was compensated by boric acid. J Trace Elem Med Biol 2018; 48: 246-53. [DOI:10.1016/j.jtemb.2018.04.016]
3. Alto P. Plasticizers. Chemical Economics Handbook. Stanford Research Associates (SRI) International, CA. USA. 1996.
4. Ambruosi B, Uranio MF, Sardanelli AM, Pocar P, Martino NA, Paternoster MS, et al. In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model. PLoS One 2011; 6: e27452. [DOI:10.1371/journal.pone.0027452]
5. Ashari S, Karami M, Shokrzadeh M, Ghandadi M, Ghassemi-Barghi N, Dashti A, et al. The implication of mitochondrial dysfunction and mitochondrial oxidative damage in di (2- ethylhexyl) phthalate induced nephrotoxicity in both in vivo and in vitro models. Toxicol Mech Methods 2020; 30: 427-37. [DOI:10.1080/15376516.2020.1758980]
6. Autian J. Toxicity and health threats of phthalate esters: review of the literature. Environ health perspect 1973; 4: 3-26. [DOI:10.1289/ehp.73043]
7. AuBuchon JP, Estep TN, Davey RJ. The effect of the plasticizer Diethylhexyl phthalate on the survival of stored RBCs. Blood 1988; 71: 448-52. [DOI:10.1182/blood.V71.2.448.448]
8. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003; 4: 517-29. [DOI:10.1038/nrm1155]
9. Bhat FA, Ramajayam G, Parameswari S, Vignesh RC, Karthikeyan S, Senthilkumar K, et al. Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts-in vitro. Toxicol in Vitro 2013; 27: 250-56. [DOI:10.1016/j.tiv.2012.09.003]
10. Chiu CY, Sun SC, Chiang CK, Wang CC, Chan DC, Chen HJ, et al. Plasticizer di (2-ethylhexyl) phthalate interferes with osteoblastogenesis and adipogenesis in a mouse. Model J Orthop Res 2018; 26: 1124-34. [DOI:10.1002/jor.23740]
11. De Sousa EB, Casado PL, Neto VM, Leite Duarte ME, Aguiar DP. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and herapeutic perspectives. Stem Cell Res Ther 2014; 5: 112. [DOI:10.1186/scrt501]
12. Dhanya CR, Indu AR, Deepadevi KV, Kurup PA. Inhibition of membrane Na+-K+ ATPase of the brain, liver and RBC in rats administered di (2-ethyl hexyl) phthalate (DEHP) a plasticizer used in polyvinyl chloride (PVC) blood storage bags. Indian J Exp Biol 2003; 41: 814-20.
13. Eslaminejad MB. Mesenchymal stem cell: isolation and biology. J Iranian Anatom Sci 2007; 5: 61-73.
14. Gross SR, Kinzy TG. Improper organization of the actin cytoskeleton affects protein synthesis at initiation. Mol Cell Biol 2007; 27: 1974-89. [DOI:10.1128/MCB.00832-06]
15. Gu Y, Gao M, Zhang W, Yan L, Shao F, Zhou J. Exposure to phthalates DEHP and DINP May lead to oxidative damage and lipidomic disruptions in mouse kidney. Chemosphere 2021; 271: 129740. [DOI:10.1016/j.chemosphere.2021.129740]
16. Hajnóczky G, Csordás G, Das S, Garcia-Perez C, Saotome M, Roy SS, et al. Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca 2+ uptake in apoptosis. Cell Calcium 2006; 40: 553-60. [DOI:10.1016/j.ceca.2006.08.016]
17. Hillman LS, Goodwin SL, Sherman WR. Identification and measurement of plasticizer in neonatal tissues after umbilical catheters and blood products. N Engl J Med 1975; 292: 381-6. [DOI:10.1056/NEJM197502202920801]
18. Huber WW, Grasl-Kraupp, B, Schulte-Hermann R. Hepatocarcinogenic potential of di (2- ethylhexyl) phthalate in rodents and its implications on human risk. Crit Rev Toxicol 1996; 26: 365-81. [DOI:10.3109/10408449609048302]
19. Hucho T, Levine JD. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 2007; 55: 365-76. [DOI:10.1016/j.neuron.2007.07.008]
20. International Programme on Chemical Safety (IPCS). 1992. Environmental health criteria 131: diethylhexyl phthalate. Geneva: World Health Organization.
21. Jaeger RJ, Rubin RJ. Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tissues. N Engl J Med 1972; 287: 1114-18. [DOI:10.1056/NEJM197211302872203]
22. Jaeger R, Rubin R. Plasticisers from PVC. The Lancet 1970; 296: 778-82. [DOI:10.1016/S0140-6736(70)90261-8]
23. Kanno S, Hirano S, Kayama F. Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells. Toxicology 2004; 196: 137-45. [DOI:10.1016/j.tox.2003.12.002]
24. Kluwe WM. Overview of phthalate ester pharmacokinetics in mammalian species. Environ Health Perspect 1982; 45: 3-10. [DOI:10.1289/ehp.82453]
25. Lin F. Adipose tissue-derived mesenchymal stem cells: a fat chance of curing kidney disease? Kidney Int 2012; 82: 731-3. [DOI:10.1038/ki.2012.158]
26. Liu JC, Li L, Yan HC, Zhang T, Zhang P, Sun ZY, et al. Identification of oxidative stress-related Xdh gene as a di(2-ethylhexyl)phthalate (DEHP) target and the use of melatonin to alleviate the DEHP-induced impairments in newborn mouse ovaries. J Pineal Res 2019; 67: e12577. [DOI:10.1111/jpi.12577]
27. Liu PS, Chen CY. Butyl benzyl phthalate suppresses the ATP-induced cell proliferation in human osteosarcoma HOS cells. Toxicol Appl Pharmacol 2010; 244: 308-14. [DOI:10.1016/j.taap.2010.01.007]
28. Lundberg G, Nilsson C. Phthalic acid esters used as plastic additives. Swedish National Chemicals Inspectorate. Solna, Sweden. 1994.
29. Magee AI, Lytton NA, Watt FM. Calcium-induced changes in cytoskeleton and motility of cultured human keratinocytes. Exp Cell Res 1987; 172: 43-53. [DOI:10.1016/0014-4827(87)90091-7]
30. Marchetti L, Sabbieti MG Menghi M, Materazzi S, Hurley MM, Menghi G. Effects of phthalate esters on actin cytoskeleton of Py1a rat osteoblasts. Histol Histopathol 2002; 17: 1061-6.
31. Nass LI, Heiberger CA. Encyclopedia of PVC. Resin Manufacture and Properties. New York and Basel, 271. 1976.
32. Palleschi S, Rossi B, Diana L, Silvestroni L. Di (2-ethylhexyl) phthalate stimulates Ca 2+ entry, chemotaxis and ROS production in human granulocytes. Toxicol Let 2009; 187: 52-7. [DOI:10.1016/j.toxlet.2009.01.031]
33. Rock G, Labow RS, Tocchi M. Distribution of di (2-ethylhexyl) phthalate and products in blood and blood components. Environ Health Perspect 1986; 65: 309-16. [DOI:10.1289/ehp.8665309]
34. Sabbieti MG, Agas D, Santoni G, Materazzi S, Menghi G, Marchetti L. Involvement of p53 in phthalate effects on mouse and rat osteoblasts. J Cell Biochem 2009; 107: 316-27. [DOI:10.1002/jcb.22127]
35. Siddiqui A, Srivastava SP. Effect of di (2-ethylhexyl) phthalate administration on rat sperm count and on sperm metabolic enzymes. Bull Environ Contam Toxicol 1992; 48: 115-19. [DOI:10.1007/BF00197492]
36. Singh Rowdhwal SS, Chen J. Toxic effects of Di-2-ethylhexyl Phthalate: an overview. Biomed Res Int 2018. [DOI:10.1155/2018/1750368]
37. European :union: risk assessment report bis-(2-ethylhexyl) phthalate (DEHP). 2008; VOL 80, 2nd priority list. Sweden.
38. Tripathi A, Pandey V, Sahu AN, Singh A, Dubey PK. Di-(2-ethylhexyl) phthalate (DEHP) inhibits steroidogenesis and induces mitochondria-ROS mediated apoptosis in rat ovarian granulosa cells. Toxicol Res 2019; 8: 381-94. [DOI:10.1039/C8TX00263K]
39. Wang Y, Wang T, Ban Y, Shen C, Shen Q, Chai X, et al. Di-(2-ethylhexyl) Phthalate exposure modulates antioxidant enzyme activity and gene expression in juvenile and adult daphnia magna. Arch Environ Contam Toxicol 2018; 75: 145-56. [DOI:10.1007/s00244-018-0535-9]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.