Heat-Cured Methyl Methacrylate Induces Increased Expression of HSP70 and iNOS in the Liver
Creators
- 1. Department of Applied Dental Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan.
- 2. Department of Anatomy, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
- 3. Department of Forensic Medicine, Legal Medicine and Toxicology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
Description
Introduction: Exposure to methyl methacrylate (MMA), which is a widely used monomer in dental and medical fields, has been shown to be associated with adverse health effects on liver. Aim: This study aims to evaluate the mechanism toxic effect of MMA on liver, via investigating alterations in the expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein70 (HSP70) in the liver, subsequent to the oral administration of MMA in rats. Methods: 20 Sprague-Dawley female rats were randomly selected and divided into two groups: control group, and experimental group. The experimental group was orally administered 120 mg/kg of MMA daily 5 times per week for four weeks. Changes in the expression of HSP70 and iNOS in the liver tissue was investigated using Immunohistochemistry technique. Results: Exp group had statistcaly higher hepatic expression of iNOS (p < 0.01) in comparison to the control group, by approximately three folds. Similarly, rat hepatocytes in the experimental group showed statistically significant (p < 0.01) increase, by approximately 15 folds, in the expression of HSP70 compared to that in the control group. Conclusion: The presented data suggest that exposure to MMA might cause liver injury as indicated by the prominanat elevation of the oxidative stress biomarker iNOS and the biological stress biomarker HSP70.
Abstract (English)
Introduction: Exposure to methyl methacrylate (MMA), which is a widely used monomer in dental and medical fields, has been shown to be associated with adverse health effects on liver. Aim: This study aims to evaluate the mechanism toxic effect of MMA on liver, via investigating alterations in the expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein70 (HSP70) in the liver, subsequent to the oral administration of MMA in rats. Methods: 20 Sprague-Dawley female rats were randomly selected and divided into two groups: control group, and experimental group. The experimental group was orally administered 120 mg/kg of MMA daily 5 times per week for four weeks. Changes in the expression of HSP70 and iNOS in the liver tissue was investigated using Immunohistochemistry technique. Results: Exp group had statistcaly higher hepatic expression of iNOS (p < 0.01) in comparison to the control group, by approximately three folds. Similarly, rat hepatocytes in the experimental group showed statistically significant (p < 0.01) increase, by approximately 15 folds, in the expression of HSP70 compared to that in the control group. Conclusion: The presented data suggest that exposure to MMA might cause liver injury as indicated by the prominanat elevation of the oxidative stress biomarker iNOS and the biological stress biomarker HSP70.
Files
IJTPR,Vol9,Issue2,Article2.pdf
Files
(579.7 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:92aaffcd682443bc06e96a1e798b127a
|
579.7 kB | Preview Download |
Additional details
Dates
- Accepted
-
2017-05-01
Software
References
- 1. Hill, R.G., The crosslinking agent ethylene glycol dimethacrylate content of the currently available acrylic denture base resins. J Dent Res, 1981. 60(3): p. 725-6. 2. Leggat, P.A., D.R. Smith, and U. Kedjarune, Surgical applications of methyl methacrylate: a review of toxicity. Arch Environ Occup Health, 2009. 64(3): p. 207-12. 3. Borak, J., et al., Methyl methacrylate and respiratory sensitization: a critical review. Crit Rev Toxicol, 2011. 41(3): p. 230-68. 4. Leggat, P.A., et al., Occupational hygiene practices of dentists in southern Thailand. Int Dent J, 2001. 51(1): p. 11-6. 5. Aydin, O., et al., The effects of methyl methacrylate on nasal cavity, lung, and antioxidant system (an experimental inhalation study). Toxicol Pathol, 2002. 30(3): p. 350-6. 6. Azhar, D.A., et al., Evaluation of methyl methacrylate monomer cytotoxicity in dental lab technicians using buccal micronucleus cytome assay. Dent Mater J, 2013. 32(3): p. 519-21. 7. Kuehn, K.D., W. Ege, and U. Gopp, Acrylic bone cements: mechanical and physical properties. Orthop Clin North Am, 2005. 36(1): p. 29-39, v-vi. 8. Kuehn, K.D., W. Ege, and U. Gopp, Acrylic bone cements: composition and properties. Orthop Clin North Am, 2005. 36(1): p. 17-28, v. 9. Lloyd, A.W., R.G. Faragher, and S.P. Denyer, Ocular biomaterials and implants. Biomaterials, 2001. 22(8): p. 769-85. 10.Cho, Y.R. and A.K. Gosain, Biomaterials in craniofacial reconstruction. Clin Plast Surg, 2004. 31(3): p. 377-85, v. 11.Hossler, F.E. and J.E. Douglas, Vascular Corrosion Casting: Review of Advantages and Limitations in the Application of Some Simple Quantitative Methods. Microsc Microanal, 2001. 7(3): p. 253-264. 12.Sham, A.S., et al., Color stability of provisional prosthodontic materials. J Prosthet Dent, 2004. 91(5): p. 447-52. 13.Aydin, O., et al., The effects of methyl methacrylate on nasal cavity, lung, and antioxidant system (an experimental inhalation study). Toxicologic pathology, 2002. 30(3): p. 350-356. 14.EPA, Methyl Methacrylate: Fact Sheet U.E.P. Agency, Editor. 1994, US Environmental Protection Agency: Washington, DC. 15.EU, uropean Union Risk Assessment Report: Methyl Methacrylate., E. Communities, Editor. 2002: Luxembourg. 16.Schlegel, U.J., et al., Pre-packed vacuum bone cement mixing systems. A further step in reducing methylmethacrylate exposure in surgery. Annals of occupational hygiene, 2010. 54(8): p. 955-961. 17.Moeen, F., Y.H. Khan, and F. Ghani, Safety And Hazards Of Materials Used In The Fabrication Of Dental Prostheses. J Pak Mater Soc 2008. 2(1): p. 6. 18.Ruyter, I.E. and H. Oysaed, Conversion in denture base polymers. J Biomed Mater Res, 1982. 16(5): p. 741-54. 19.Stafford, G.D. and S.C. Brooks, The loss of residual monomer from acrylic orthodontic resins. Dent Mater, 1985. 1(4): p. 135-8. 20.Huang, F.-M., et al., Residual monomer releasing from acrylic denture base in water. Chinese Dental Journal, 2000. 19(1): p. 17-22. 21.Pfeiffer, P. and E.U. Rosenbauer, Residual methyl methacrylate monomer, water sorption, and water solubility of hypoallergenic denture base materials. J Prosthet Dent, 2004. 92(1): p. 72-8. 22.Jolly, C. and R.I. Morimoto, Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst, 2000. 92(19): p. 1564-72. 23.Georgopoulos, C. and W.J. Welch, Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol, 1993. 9: p. 601-34. 24.Bukau, B., J. Weissman, and A. Horwich, Molecular chaperones and protein quality control. Cell, 2006. 125(3): p. 443-51. 25.Jaenicke, R., What does protein refolding in vitro tell us about protein folding in the cell? Philos Trans R Soc Lond B Biol Sci, 1993. 339(1289): p. 287-94; discussion 294-5. 26.Hartl, F.U., Molecular chaperones in cellular protein folding. Nature, 1996. 381(6583): p. 571-9. 27.Bratt, J.M., et al., Competitive metabolism of Larginine: arginase as a therapeutic target in asthma. J Biomed Res, 2011. 25(5): p. 299-308. 28.Juurlink, B.H., Management of oxidative stress in the CNS: the many roles of glutathione. Neurotox Res, 1999. 1(2): p. 119-40. 29.Fialkow, L., Y. Wang, and G.P. Downey, Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med, 2007. 42(2): p. 153-64. 30.Zhao, W., D.I. Diz, and M.E. Robbins, Oxidative damage pathways in relation to normal tissue injury. Br J Radiol, 2007. 80 Spec No 1: p. S23-31. 31.Pall, M.L., Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO- cycle. Med Hypotheses, 2007. 69(4): p. 821-5. 32.Mikkelsen, R.B. and P. Wardman, Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms. Oncogene, 2003. 22(37): p. 5734-54. 33.Lee, J.H., E.S. Yang, and J.W. Park, Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury. J Biol Chem, 2003. 278(51): p. 51360-71. 34.Elovaara, E., H. Kivisto, and H. Vainio, Effects of methyl methacrylate on non-protein thiols and drug metabolizing enzymes in rat liver and kidneys. Arch Toxicol, 1983. 52(2): p. 109-21. 35.Pradhan, L., et al., Effect of binge cocaine treatment on hindlimb vascular function. J Appl Toxicol, 2005. 25(6): p. 479-90. 36.Erekat, N., A. Al Khatib, and M. Al-Jarrah, Endurance Exercise Training Attenuates the up Regulation of iNOS in the Skeletal Muscles of Chronic/Progressive Mouse Model of Parkinson's Disease. Journal of Neurology Research, 2013. 3(3-4): p. 108-113. 37.Erekat, N.S., Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease. The Anatomical Record, 2015. 298(8): p. 1472-1478. 38.Lanneau, D., et al., Heat shock proteins: essential proteins for apoptosis regulation. J Cell Mol Med, 2008. 12(3): p. 743-61. 39.Gupta, S.C., et al., Heat shock proteins in toxicology: how close and how far? Life Sci, 2010. 86(11-12): p. 377-84. 40.Simpson, S.A., D.J. Alexander, and C.J. Reed, Induction of heat shock protein 70 in rat olfactory epithelium by toxic chemicals: in vitro and in vivo studies. Arch Toxicol, 2005. 79(4): p. 224-30. 41.Ansteinsson, V., et al., Cell toxicity of methacrylate monomers-the role of glutathione adduct formation. J Biomed Mater Res A, 2013. 101(12): p. 3504-10. 42.Ozen, O.A., et al., Effect of formaldehyde inhalation on Hsp70 in seminiferous tubules of rat testes: an immunohistochemical study. Toxicol Ind Health, 2005. 21(10): p. 249-54. 43.Siddique, Y.H. and M. Afzal, Protective effects of apigenin against methyl methanesulfonate induced hsp70 expression in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9). J Pharmacol Pharmacother, 2012. 3(2): p. 188-90. 44.La Porte, P.F., Mytilus trossulus hsp70 as a biomarker for arsenic exposure in the marine environment: laboratory and real-world results. Biomarkers, 2005. 10(6): p. 417-28. 45.Young, J.C., Mechanisms of the Hsp70 chaperone system. Biochem Cell Biol, 2010. 88(2): p. 291-300. 46.Kleinert, H., et al., Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol, 2004. 500(1-3): p. 255-66. 47.Guzik, T.J., et al., Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension, 2002. 39(6): p. 1088-94. 48.Channon, K.M. and T.J. Guzik, Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors. J Physiol Pharmacol, 2002. 53(4 Pt 1): p. 515-24. 49.Liu, J. and M.P. Waalkes, Nitric oxide and chemically induced hepatotoxicity: beneficial effects of the liverselective nitric oxide donor, V-PYRRO/NO. Toxicology, 2005. 208(2): p. 289-97. 50.Jaeschke, H., et al., Mechanisms of hepatotoxicity. Toxicol Sci, 2002. 65(2): p. 166-76. 51.Li, J. and T.R. Billiar, IV. Determinants of nitric oxide protection and toxicity in liver. Vol. 276. 1999. G1069- G1073.