Skip to main content
SpringerLink
Log in

Monosodium Glutamate Induces Cytotoxicity in Rat Liver via Mitochondrial Permeability Transition Pore Opening

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Monosodium glutamate (MSG) is a major food additive used as a flavor enhancer. A lot of controversies have been generated over the use of MSG. The present study therefore investigated whether MSG would induce cytotoxicity via the induction of mitochondrial permeability transition (mPT) pore opening. 36 male albino rats were used for this study. The rats were equally divided into six groups: group I is the control while group II, III, IV, V, and VI were orally treated with MSG (25, 50, 100, 200, and 400 mg/kg) daily for 28 days. The opening of the pore, cytochrome c release, mitochondrial ATPase activity, mitochondrial lipid peroxidation and hepatic DNA fragmentation were determined spectrophotometrically. Histological assessment of prostate and brain was carried out. The results show that MSG at concentrations ≤30 µg/ml did not induce mPT pore opening while higher concentrations caused significant induction of pore opening. Also, at lower doses (25 and 50 mg/kg), MSG did not cause any significant induction of mPT pore opening while at higher doses, there were significant induction of pore opening. Similar trend of results was recorded for cytochrome c release, mitochondrial ATPase activity and lipid peroxidation. The histological results show that at low doses (25 and 50 mg/kg), no significant lesion was observed while higher doses caused benign prostatic hyperplasia (BPH) in the prostate and necrotic damage in the brain. MSG administration at low dose is tolerable while high doses induce cytotoxicity via mPT pore opening.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Özlem, S. A. (2017). In vitro cytotoxicity and cell viability assays: principles, advantages, and disadvantages, genotoxicity-a predictable risk to our actual world, Marcelo L. Larramendy and Sonia Soloneski, IntechOpen. https://doi.org/10.5772/intechopen.71923.

  2. Yuan, L., & Kaplowitz, N. (2013). Mechanisms of drug induced liver injury. Clinics in Liver Disease, 17(4), 507–518.

    Article  Google Scholar 

  3. Bernardi Pand Di Lisa, F. (2015). The mitochondrial permeability transition pore: Molecular nature and role as a target in cardioprotection. Journal of Molecular and Cellular Cardiology, 78, 100–106.

    Article  Google Scholar 

  4. Martins, K. R. (2006). Targeting apoptosis with dietary bioactive agents. Minireview, 2006, 117–130.

    Google Scholar 

  5. Olowofolahan, A. O., Bolarin, O. L., & Olorunsogo, O. O. (2020). In vitro and in vivo effect of 3-Para-fluorobenzoyl-propionic acid on rat liver mitochondrial permeability transition pore opening and lipid peroxidation. Annals of Science and Technology, 5(1), 39–44.

    Article  Google Scholar 

  6. Elkholi, R., Renault, T. T., Serasinghe, M. N., & Chipuk, J. E. (2014). Putting the pieces together: how is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy? Cancer Metabolism, 2, 16.

    Article  Google Scholar 

  7. Golstein, P., & Kroemer, G. (2007). Cell death by necrosis: towards a molecular definition. Trends in Biochemical Sciences, 32, 37–43.

    Article  CAS  Google Scholar 

  8. Supnet, C., & Bezprozvanny, I. (2010). Neuronal calcium signaling, mitochondrial dysfunction, and Alzheimer’s disease. Journal of Alzheimer’s Disease, 20(2), 487–498.

    Article  Google Scholar 

  9. Kwong, JenniferQ., & Molkentin, JefferyD. (2014). Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metabolism. https://doi.org/10.1016/j.cmet.2014.12.001.

    Article  Google Scholar 

  10. Javadov, S., & Karmazyn, M. (2007). Mitochondrial permeability transition pore as end point to cell death and as a putative target for cardioprotection. Cellulor Physiology and Biochemistry, 20, 1–22.

    Article  CAS  Google Scholar 

  11. Izzo, V., Pedro, J. M., Kroemer, V. G., & Galluzzi, L. (2016). Mitochondrial permeability transition: new findings and persisting uncertainties. Trends in Cell Biology, 26(9), 655–667.

    Article  CAS  Google Scholar 

  12. Obochi, G., Malu, S., Obi-Abang, M., Alozie, Y., & Iyam, M. (2009). Effect of garlic extracts on monosodium glutamate (MSG) induced fibroid in wistar rats. Pakistan Journal of Nutrition, 8(7), 970–976.

    Article  CAS  Google Scholar 

  13. Olowofolahan, A. O., Aina, O. O., Hassan, E. T., & Olorunsogo, O. O. (2017). Ameliorative potentials of methanol extract and chloroform fraction of drymaria cordata on MSG induced uterine hyperplasia in female wistar rats. European Journal of Medicinal Plants., 20(4), 1–9.

    Article  Google Scholar 

  14. Johnson, D., & Lardy, H. (1967). Isolation of liver or kidney mitochondria. Methods Enzymology, 10, 94–96.

    Article  CAS  Google Scholar 

  15. Olorunsogo, O. O., Bababunmi, E. A., & Bassir, O. (1979). Uncoupling effect of N-phosphonomethylglycine on rat liver mitochondria. Biochemical Pharmacology, 27, 925–927.

    Google Scholar 

  16. Lapidus, R. G., & Sokolove, P. M. (1993). Inhibition by spermine of the inner membrane permeability transition of isolated heart mitochondria. FEBS. Letters, 3, 314–318.

    Google Scholar 

  17. Lowry, O. H., Rosenbrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with Folin phenol reagent. Journal of Biological Chemistry, 1951(193), 265–27.

    Google Scholar 

  18. Olorunsogo, O. O., & Malomo, S. O. (1985). Sensitivity of Oligomycin-inhibitedrespiration of isolated rat liver mitochondriato perfluidone, a fluorinated arylalkylsulfonamide. Toxicology, 35(3), 231–240.

    Article  CAS  Google Scholar 

  19. Bassir, O. (1963). Improving the level of of nutrition. West African Journal of Biology and Applied Chemistry, 7, 32–40.

    Google Scholar 

  20. Appaix, F., Minatchy, M., Riva-Lavieille, C., Olivaires, J., Antonnson, B., & Saks, V. A. (2000). Rapid spectrophotometric method for quantitation of cyctochrome c release from isolated mitochondria or permealized cells revisited. Biochimica et Biophysica Acta, 1457, 175–181.

    Article  CAS  Google Scholar 

  21. Varshney, R., & Kale, R. K. (1990). Effect of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. International Journal of Radiation Biology, 58, 773–743.

    Article  Google Scholar 

  22. Wu, B., Ootani, A., Iwakiri, R., Sakata, Y., Fujise, T., Amemori, S., Yokoyama, F., Tsunada, S., Toda, S., & Fujimoto, K. (2006). T cell deficiency leads to liver carcinogenesis in azoxymethane-treated rats. Experimental Biology and Medicine, 231, 91–98.

    Article  CAS  Google Scholar 

  23. Kroemer, G., Galluzzi, L., & Brenner, C. (2007). Mitochondrial membrane permeabilization in cell death. Physiological Reviews, 87, 99–163.

    Article  CAS  Google Scholar 

  24. Tait, S. W., & Green, D. R. (2010). Mitochondria and cell death: outer membrane permeabilization and beyond. Nature Reviews Molecular Cell Biology, 11, 621–632.

    Article  CAS  Google Scholar 

  25. Green, D. R., & Kroemer, G. (2004). The pathophysiology of mitochondrial cell death. Science, 305, 626–629.

    Article  CAS  Google Scholar 

  26. Kroemer, G., & Reed, J. C. (2000). Mitochondrial control of cell death. Nature Medicine, 6, 513–519.

    Article  CAS  Google Scholar 

  27. Angelin, A., Bonaldo, P., & Bernardi, P. (2008). Altered threshold of the mitochondrial permeability transition pore in Ullrich congenital muscular dystrophy. Biochimica et Biophysica acta, 1777, 893–896.

    Article  CAS  Google Scholar 

  28. Seidlmayer, L. K., Gomez-Garcia, M. R., Blatter, L. A., Pavlov, E., & Dedkova, E. N. (2012). Inorganic polyphosphate is a potent activator of the mitochondrial permeability transition pore in cardiac myocytes. The Journal of General Physiology, 139, 321–331.

    Article  CAS  Google Scholar 

  29. Halestrap, A. P. (2009). What is the mitochondrial permeability transition pore? Journal of Molecular and Cellulor Cardiology, 46, 821–831.

    Article  CAS  Google Scholar 

  30. Farombi, E. O., & Onyema, O. O. (2006). Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin. Human and Experimental Toxicology, 5, 251–259.

    Article  Google Scholar 

  31. Olowofolahan, A. O., Adeosun, O. A., Afolabi, O. T., & Olorunsogo, O. O. (2018). Effect of methanol extract of Mangifera indica on mitochondrial membrane permeability transition pore in normal rat liver and monosodium glutamate-induced liver and uterine damage. Journal of Complementary and Alternative Medicalÿ Research, 5, 1–14.

    Article  CAS  Google Scholar 

Download references

Author Contributions

Conceptualization: A.O.O.; Methodology: A.O.O. and O.A.A., Formal analysis and investigation: A.O.O. and O.A.A.; Writing - review and editing: A.O.O.; Funding acquisition: Nil; Supervision: O.O.O. All the authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Adeola Oluwakemi Olowofolahan, Oluwatobi Andrew Adeosun & Olufunso Olabode Olorunsogo

Authors
  1. Adeola Oluwakemi Olowofolahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oluwatobi Andrew Adeosun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olufunso Olabode Olorunsogo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adeola Oluwakemi Olowofolahan.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Olowofolahan, A.O., Adeosun, O.A. & Olorunsogo, O.O. Monosodium Glutamate Induces Cytotoxicity in Rat Liver via Mitochondrial Permeability Transition Pore Opening. Cell Biochem Biophys 78, 429–437 (2020). https://doi.org/10.1007/s12013-020-00944-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-020-00944-z

Keywords

Search

Navigation