THE EFFECTS OF VITAMIN C ON GLYCIDAMIDE-INDUCED CELLULAR DAMAGE AND APOPTOSIS IN MOUSE LEYDIG CELLS

Year 2019, Volume: 20 Issue: 1, 9 - 17, 15.04.2019

Banu Orta Yılmaz

https://doi.org/10.23902/trkjnat.454020

Abstract

The aim of this study was to elucidate the role
of vitamin C on glycidamide-induced cytotoxicity, oxidative damage and cell
death in Leydig (TM3) cells. Leydig cells were exposed to glycidamide (1, 10,
100 and 1000 μM) and/or vitamin C (50 μM) for 24 h. After completion of the
exposure time, cell viability, amount of lactate dehydrogenase enzyme,
apoptosis-necrosis rates, levels of oxidative stress parameters such as
hydroxyl radical, hydrogen peroxide and lipid peroxidation were determined in
Leydig cells. The results showed that glycidamide administration decreased
Leydig cell viability and increased cytotoxicity significantly at high
concentration (1000 μM). In addition, glycidamide generated oxidative damage by
significantly increasing the production of reactive oxygen species and lipid
peroxidation. Exposure to glycidamide increased the formation of early
apoptosis, apoptosis and necrosis in Leydig cells. Consequently, glycidamide
has been shown to cause apoptosis due to lipid peroxidation and formation of
reactive oxygen species in Leydig cells, and vitamin C has a therapeutic role
against toxicity caused by glycidamide.

Keywords

Glycidamide, cytotoxicity, oxidative stress, Vitamin C, Leydig cell, apoptosis

References

• 1. Albalawi, A., Alhasani, R.H.A., Biswas, L., Reilly, J. & Shu, X. 2017. Protective effect of carnosic acid against acrylamide-induced toxicity in RPE cells. Food and Chemical Toxicology, 108: 543-553.
• 2. Alturfan, E.I., Beceren, A., Sehirli, A.O., Demiralp, Z.E., Sener, G. & Omurtag, G.Z. 2012. Protective effect of N-acetyl-L-cysteine against acrylamide induced oxidative stress in rats. Turkish Journal of Veterinary and Animal Sciences, 36(4): 438-445.
• 3. Baba, N.A., Raina, R., Verma, P.K., Sultana, M., Prawez, S. & Nisar, N.A. 2013. Toxic effects of fluoride and chlorpyrifos on antioxidant parameters in rats: protective effects of vitamin C and E. Fluoride, 46(2):73-9.
• 4. Bandarra, S., Fernandes, A.S., Magro, I., Guerreiro, P.S., Pingarilho, M., Churchwell, M.I., Gil, O.M., Batinić-Haberle, I., Gonçalves, S., Rueff, J., Miranda, J.P., Marques, M.M., Beland, F.A., Castro, M., Gaspar, J.F. & Oliveira, N.G. 2013. Mechanistic insights into the cytotoxicity and genotoxicity induced by glycidamide in human mammary cells. Mutagenesis, 28(6): 721-729.
• 5. Baum, M., Fauth, E., Fritzen, S., Herrmann, A., Mertes, P., Merz, K., Rudolphi, M., Zankl, H. & Eisenbrand, G. 2005. Acrylamide and glycidamide: genotoxic effects in V79-cells and human blood. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 580(1): 61-69.
• 6. Camacho, L., Latendresse, J.R., Muskhelishvili, L., Patton, R., Bowyer, J.F., Thomas, M. & Doerge, D.R. 2012. Effects of acrylamide exposure on serum hormones, gene expression, cell proliferation, and histopathology in male reproductive tissues of Fischer 344 rats. Toxicology Letters, 211(2): 135-143.
• 7. Chang, I.S., Jin, B., Youn, P., Park, C., Park, J.D. & Ryu, D.Y. 2007. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis. Toxicology and Applied Pharmacology, 218(2): 196-203.
• 8. Chen, J.H., Wu, K.Y., Chiu, M., Tsou, T.C. & Chou, C.C. 2009. Acrylamide-induced astrogliotic and apoptotic responses in human astrocytoma cells. Toxicology in Vitro, 23(5): 855-861.
• 9. Chen, J.H., Yang, C.H., Wang, Y.S., Lee, J.G., Cheng, C.H. & Chou, C.C. 2013. Acrylamide-induced mitochondria collapse and apoptosis in human astrocytoma cells. Food and Chemical Toxicology, 51: 446-452.
• 10. Das, U.B., Mallick, M., Debnath, J.M. & Ghosh, D. 2002. Protective effect of ascorbic acid on cyclophosphamide-induced testicular gametogenic and androgenic disorders in male rats. Asian Journal of Andrology, 4(3): 201-208.
• 11. Devasagayam, T.P. & Tarachand, U. 1987. Decreased lipid peroxidation in the rat kidney during gestation. Biochemical and Biophysical Research Communications, 145: 134-138.
• 12. Elghaffar, S.K.A., Fiedan, I.O., Ahmed, E.A. & Omar, H.E.D.M. 2015. Acrylamide Induced Testicular Toxicity in Rats: Protective Effect of Garlic Oil. Biomarkers, 1(1): 5.
• 13. World Health Organization. 2002. Health Implications of Acrylamide in Food: Report of a Joint FAO/ WHO Consultation WHO Headquarters. Geneva, Switzerland. PDF version available at: http://apps.who.int/iris/bitstream/10665/42563/1/9241562188.pdf. (Date accessed: May 2017).
• 14. Fennell, T.R., Sumner, S.C.J., Snyder, R.W., Burgess, J., Spicer, R., Bridson, W.E. & Friedman, M. 2005. Metabolism and hemoglobin adduct formation of acrylamide in human. Toxicological Sciences, 85: 447-59.
• 15. Friedman, M. 2015. Acrylamide: inhibition of formation in processed food and mitigation of toxicity in cells, animals, and humans. Food & Function, 6(6): 1752-1772.
• 16. Haider, S.G. 2004. Cell Biology of Leydig Cells in the Testis. International Review of Cytology, 233: 181-241.
• 17. Hamdy, S.M., Bakeer, H.M., Eskander, E.F. & Sayed, O.N. 2012. Effect of acrylamide on some hormones and endocrine tissues in male rats. Human & Experimental Toxicology, 31(5): 483-491.
• 18. Holland, M.K. & Storey, B.T. 1981. Oxygen metabolism of mammalian spermatozoa. Generation of hydrogen peroxide by rabbit epididymal spermatozoa. Biochemical Journal, 198: 273-280.
• 19. IARC. 1994. Acrylamide In IARC Monographs on the Evaluation of Carcinogenic Risk to Humans, International Agency for Research on Cancer, 60: 389-433.
• 20. International Agency for Research on Cancer (IARC). 1994. Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Industrial Chemicals.IARC, Lyon, France.
• 21. Kacar, S., Vejselova, D., Kutlu, H.M. & Sahinturk, V. 2018. Acrylamide-derived cytotoxic, anti-proliferative, and apoptotic effects on A549 cells. Human & experimental toxicology, 37(5): 468-474.
• 22. Lee, J.G., Wang, Y.S. & Chou, C.C. 2014. Acrylamide-induced apoptosis in rat primary astrocytes and human astrocytoma cell lines. Toxicology in Vitro, 28(4): 562-570.
• 23. Levine, M., Rumsey, S.C., Daruwala, R., Park, J.B. & Wang, Y. 1999. Criteria and recommendations for vitamin C intake. Jama, 281(15): 1415-1423.
• 24. Li, M., Sun, J., Zou, F., Bai, S., Jiang, X., Jiao, R. & Bai, W. 2017. Glycidamide inhibits progesterone production through reactive oxygen species-induced apoptosis in R2C Rat Leydig Cells. Food and Chemical Toxicology, 108: 563-570.
• 25. Lingnert, H., Grivas, S., Jägerstad, M., Skog, K., Törnqvist, M. & Åman, P. 2002. Acrylamide in food: mechanisms of formation and influencing factors during heating of foods. Scandinavian Journal of Nutrition, 46(4): 159-172.
• 26. Ma, Y., Shi, J., Zheng, M., Liu, J., Tian, S., He, X., Zhang, D., Li, G. & Zhu, J. 2011. Toxicological effects of acrylamide on the reproductive system of weaning male rats. Toxicology and industrial health, 27(7): 617-627.
• 27. Martins, C., Oliveira, N.G., Pingarilho, M., Gamboa da Costa, G., Martins, V., Marques, M.M., Beland, F.A., Churchwell, M.I., Doerge., D.R. & Gaspar, J.F. 2006. Cytogenetic damage induced by acrylamide and glycidamide in mammalian cells: correlation with specific glycidamide-DNA adducts. Toxicological Sciences, 95(2): 383-390.
• 28. Mottram, D.S., Wedzicha, B.L. & Dodson, A.T. 2002. Food chemistry: acrylamide is formed in the Maillard reaction. Nature, 419:448-449.
• 29. Orta, B. & Erkan, M. 2014. Effects of vitamin c on antioxidant systems and Steroidogenic enzymes in sodium fluoride exposed Tm4 sertoli cells. Fluoride, 47(2): 139-151.
• 30. Padayatty, S.J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J.H., Chen, S., Corpe, C., Dutta, A., Dutta, S.H. & Levine, M. 2003. Vitamin C as an antioxidant: evaluation of its role in disease prevention. Journal of the American college of Nutrition, 22(1): 18-35.
• 31. Paulsson, B., Grawé, J. & Törnqvist, M. 2002. Hemoglobin adducts and micronucleus frequencies in mouse and rat after acrylamide or N-methylolacrylamide treatment. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 516(1): 101-111.
• 32. Puntarulo, S. & Cederbaum, A.I. 1988. Effect of oxygen concentration on microsomal oxidation of ethanol and generation of oxygen radicals. Biochemical Journal, 251: 787-794.
• 33. Sen, E., Tunali, Y. & Erkan, M. 2015. Testicular development of male mice offsprings exposed to acrylamide and alcohol during the gestation and lactation period. Human & Experimental Toxicology, 34(4): 401-414.
• 34. Shrivastava, S., Uthra, C., Reshi, M., Singh, A., Yadav, D. & Shukla, S. 2018. Protective effect of hesperetin against acrylamide induced acute toxicity in rats. Indian Journal of Experimental Biology, 56: 164-170.
• 35. Soliman, G.Z. 2013. Protective effect of Solanum nigrum, vitamin C or melatonin on the toxic effect of acrylamide on rats. Journal of Pharmaceutical and Biological Sciences, 5: 47-54.
• 36. Stadler, R.H., Blank, I., Varga, N., Robert, F., Hau, J., Guy, P.A., Robert, M.C. & Riediker, S. 2002. Food chemistry: acrylamide from Maillard reaction products. Nature, 419(6906): 449.
• 37. Sun, J., Li, M., Zou, F., Bai, S., Jiang, X., Tian, L., Ou, S., Jiao, R. & Bai, W. 2018. Protection of cyanidin-3-O-glucoside against acrylamide-and glycidamide-induced reproductive toxicity in leydig cells. Food and Chemical Toxicology, 119: 268-274.
• 38. Taeymans, D., Wood, J., Ashby, P., Blank, I., Studer, A., Stadler, R.H., Gondé, P., Eijck, P., Lalljie, S., Lingnert, H., Lindblom, M., Matissek, R., Müller, D., Tallmadge, D., O'brien, J., Thompson, S., Silvani, D. & Lindblom, M. 2004. A review of acrylamide: an industry perspective on research, analysis, formation, and control. Critical Reviews in Food Science and Nutrition, 44(5): 323-347.
• 39. Vattem, D.A. & Shetty, K. 2003. Acrylamide in food: a model for mechanism of formation and its reduction. Innovative Food Science & Emerging Technologies, 4(3): 331-338.
• 40. Wang, H., Huang, P., Lie, T., Li, J., Hutz, R.J., Li, K. & Shi, F. 2010. Reproductive toxicity of acrylamide-treated male rats. Reproductive Toxicology, 29(2): 225-230.
• 41. Wang, E.T., Chen, D.Y., Liu, H.Y., Yan, H.Y. & Yuan, Y. 2015. Protective effect of allicin against glycidamide-induced toxicity in male and female mice. General Physiology and Biophysics, 34(2): 177-187.
• 42. Yang, H.J., Lee, S.H., Jin, Y., Choi, J.H., Han, D.U., Chae, C., Lee, M.H. & Han, C.H. 2005. Toxicological effects of acrylamide on rat testicular gene expression profile. Reproductive Toxicology, 19(4): 527-534.
• 43. Yildizbayrak, N. & Erkan, M. 2018. Acrylamide disrupts the steroidogenic pathway in Leydig cells: possible mechanism of action. Toxicological & Environmental Chemistry, 100(2): 235-246.
• 44. Yilmaz, B.O., Yildizbayrak, N., Aydin, Y. & Erkan, M. 2017. Evidence of acrylamide-and glycidamide-induced oxidative stress and apoptosis in Leydig and Sertoli cells. Human & Experimental Toxicology, 36(12): 1225-1235.
• 45. Yousef, M.I. & El-Demerdash F.M. 2006. Acrylamide induced oxidative stress and biochemical perturbation in rats. Toxicology, 219: 133-141.
• 46. Zamani, E., Shokrzadeh, M., Ziar, A., Abedian-Kenari, S. & Shaki, F. 2017. Acrylamide attenuated immune tissues’ function via induction of apoptosis and oxidative stress: Protection by l-carnitine. Human & Experimental Toxicology, 37(8): 859-869.
• 47. Zhang, J.X., Yue, W.B., Ren, Y.S. & Zhang, C.X. 2010. Enhanced fat consumption potentiates acrylamide-induced oxidative stress in epididymis and epididymal sperm and effect spermatogenesis in mice. Toxicology Mechanisms and Methods, 20(2): 75-81.
• 48. Zhang, L., Wang, E., Chen, F., Yan, H. & Yuan, Y. 2013. Potential protective effects of oral administration of allicin on acrylamide-induced toxicity in male mice. Food & Function, 4(8): 1229-1236.