The Effect of Chronic Diazepam Administration on Lipid Peroxidation and Ca2+-Atpase Activity in Rat Liver

Short Communication


Chronic administration of diazepam (DZP) caused an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH) content. DZP also markedly lowered Ca2+ATPase activity. Treatment with Se plus vitamin E reduced MDA levels and increased GSH content. Our results suggest that, increased lipid peroxidation together with alteration in Ca2+-ATPase activity may play a role in DZP induced hepatic injury and Se plus vitamin E treatment may contribute to the attenuation of DZP induced hepatotoxi-city.


  1. 1.

    Barriere, M., Piriou, A., Tallineau, C., Boulard, M., Mura, P., Guettier, A., Pourrat, O. (1983) Intoxication by benzodiazepines: studies with diazepam used as a model compound suggest an interaction with red blood cells calmodulin dependent (Ca2+, Mg2+) ATPase. Toxicol. Lett. 19, 287–291.

    CAS  Article  Google Scholar 

  2. 2.

    Buege, J. A., Aust, J. D. (1978) Microsomal lipid peroxidation. Method. Enzynol. 52, 302–310.

    CAS  Article  Google Scholar 

  3. 3.

    Beutler, E., Duron, O., Kelly, B. M. (1963) Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 61, 882–888.

    CAS  PubMed  Google Scholar 

  4. 4.

    Chatterjee, S., Chatterjee, J., Chaudhur°, K., Basu, S., Maitti, C. (1997) Hepatotoxicity of diazepam: Structural and trace metal studies in rat. Biol. Trace Elem. Res. 57, 239–249.

    CAS  Article  Google Scholar 

  5. 5.

    Levin, R. M., Weiss, B. (1979) Selective binding of antipsychotics and other psychoactive agents to the calcium dependent activator of cyclic nucleotide phosphodiesterase. J. Pharmacol. Exp. Ther. 208, 454–458.

    CAS  PubMed  Google Scholar 

  6. 6.

    Lowry, O. H., Rosebrough, N. J., Forry, A. L., Randall, R. J. (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265–275.

    CAS  Google Scholar 

  7. 7.

    Musavi, S., Kakkar, P. (1998) Diazepam induced early oxidative changes at the subcellular level in rat brain. Mol. Cell Biochem. 178, 41–46.

    CAS  Article  Google Scholar 

  8. 8.

    Michiels, C., Raes, M., Toussant, O., Remacle, J. (1994) Importance of Se-glutathione peroxidase, catalase and CuZn-SOD for cell survival against oxidative stress. Free Rad. Biol. Med. 17, 235–238.

    CAS  Article  Google Scholar 

  9. 9.

    Musavi, S., Kakkar, P. (2003) Effect of diazepam treatment and its withdrawal on pro/antioxidative processes in rat brain. Mol. Cell. Biochem. 245, 51–56.

    CAS  Article  Google Scholar 

  10. 10.

    Nandhini, T. A., Anuradha, C. V. (2003) Inhibition of lipid peroxidation protein glycation and elevation of membrane ion pump activity by taurine in red blood cells exposed to high glucose. Clin. Chim. Acta 336, 129–135.

    CAS  Article  Google Scholar 

  11. 11.

    Ohkawa, H., Ohishi, N., Yagi, K. (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid. Anal. Biochem. 95, 351–358.

    CAS  Article  Google Scholar 

  12. 12.

    Ruffoli, R., Carpi, A., Giambelluca, M. A., Grasso, L., Scavuzzo, M. C., Giannessi, F. (2006) Diazepam administration prevents testostrerone decrease and lipofuscin accumulation in testis of mouse exposed to chronic noise stress. Andrologia 38, 159–165.

    CAS  Article  Google Scholar 

  13. 13.

    Shaheen, A. A., Hamdy, M. A., Kheir-Eldin, A. A., Lindstrom, P., El-Fattah, A. A. (1993) Effect of pretreatment with vitamin E or diazepam on brain metabolism of stressed rats. Biochem. Pharmacol. 46, 194–197.

    CAS  Article  Google Scholar 

  14. 14.

    Vincenzi, F. F., Hinds, T. R., Raess, B. U. (1980) Calmodulin and the plasma calcium pump. Ann. N. Y. Acad. Sci. 356, 232–244.

    CAS  Article  Google Scholar 

  15. 15.

    Yamaguchi, M. (1980) Comparison of calcitonin, epinephrine and glucagon effects on plasma membrane Ca-ATPase activity and calcium content in liver of rats. Endocrinol. Japan 27, 273–276.

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Şule Seçkin.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Cite this article

Seçkin, Ş., Alsancak, Ş., Başaran-Küçükgergin, C. et al. The Effect of Chronic Diazepam Administration on Lipid Peroxidation and Ca2+-Atpase Activity in Rat Liver. BIOLOGIA FUTURA 58, 441–443 (2007).

Download citation


  • Diazepam
  • lipid peroxidation
  • Ca2+-ATPase
  • rat liver