Advertisement

Acta Biologica Hungarica

, Volume 61, Issue 2, pp 135–144 | Cite as

Effects of Marijuana and Diazepam on Lipid Peroxidation, Na+, K+ Atpase, and Levels of Glutathione and 5-HTP in rat Brain

  • G. D. Calderón
  • Gabriela J. Esquivel
  • Ernestina H. García
  • Norma B. Osnaya
  • H. Juárez OlguínEmail author
Article

Abstract

Our aim was to evaluate the effects of marijuana (Mar) and diazepam (Dz) on lipid peroxidation (TBARS), Na+, K+ ATPase activity, levels of glutathione (GSH) and 5-hydroxytryptophan (5-HTP). Male Wistar rats were given a single dose per group: extract of Mar (100 μL/kg), Dz (5 mg/kg), Mar plus Dz, and NaCl for control. Sixty mins after treatment, animals were sacrificed, and their brains extracted and homogenised to measure GSH, TBARS and 5-HTP levels. Na+, K+ ATPase and total ATPase activities. GSH and TBARS did not show differences respect to controls. Na+, K+ ATPase activity was similar as well. However, groups treated with Mar, total ATPase activity decreased significantly (p < 0.05). Levels of 5-HTP decreased significantly (p = 0.0001) in rats treated either with Mar and or Dz. Mar and Dz induced biochemical effects on the serotonergic metabolism, which can alter the development and function in rat brain, because it has also been involved in scavenging free radicals present there.

Keywords

Brain diazepam glutathione marijuana rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgement

We thank to Dr Radames Alemon for helping us to translate the manuscript.

References

  1. 1.
    Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., Freeman, B. A. (1994) Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxides. Proc. Natl. Acad Sci. USA. 87, 1629–1634.Google Scholar
  2. 2.
    Ben de Kruijff (1987) Polymorphic regulation of membrane lipid composition. Nature 329, 587–588.CrossRefGoogle Scholar
  3. 3.
    Brase, D. A. (1990) Is intracellular sodium involved in the mechanism of tolerance to opioid drugs? Med. Hypotheses 32, 161–167.CrossRefGoogle Scholar
  4. 4.
    Calderon, G. D., Toledo, L. A., Hernandez, I. J., Barragan, M. G., Rodriguez, P. R., Hernandez, G. E. (2001) Determination de triptofano en cerebro de ratas expuestas a ozono. Arch. Neurosci. (Mex) 6, 2–5.Google Scholar
  5. 5.
    Calderon, G. D., Hernandez, I. J., Espitia, V. I., Barragan, M. G., Hernandez, G. E., Juarez Olguin, H. (2004) Pyridoxine, regardless of serotonin levels, increases production of 5-hydroxytryptophan in rat brain. Arch. Med. Res. 35, 271–274.CrossRefGoogle Scholar
  6. 6.
    Calderón, G. D., Espitia, V. I., López, D. A., Hernández, G. E., Huerta, G. B., Juarez Olguin, H. (2005) Effect of toluene and nutritional status on serotonin, lipid peroxidation levels and Na+/K+-ATPase in adult rat brain. Neurochem. Res. 30, 619–624.CrossRefGoogle Scholar
  7. 7.
    Ebadi, M., Govitrapong, P., Phansuwan-Pujito, P., Nelson, F., Reiter, R. J. (1998) Pineal opioid receptors and analgesic action of melatonin. J. Pineal Res. 24, 193–200.CrossRefGoogle Scholar
  8. 8.
    Enrico, P., Mura, M. A., Esposito, G., Serra, P., Migheli, R. (1998) Effect of naloxone on morphine-induced changes in striatal dopamine metabolism and glutamate, ascorbic acid and uric release in freely moving rats. Brain Res. 797, 94–102.CrossRefGoogle Scholar
  9. 9.
    Fernstrom, J. D., Wurtman, R. J. (1972) Brain serotonin content: Physiological regulation by plasma neutral amino acids. Science 178, 414–416.CrossRefGoogle Scholar
  10. 10.
    Fiske, C. H., Subbarow, Y. (1925) The colorimetric determination of phosphorus. J. Biol. Chem. 66, 375–400.Google Scholar
  11. 11.
    Garcia, C. A., Serrano, M., Perez, D. B., Gonzalez, V., Ormazabal, A., Pineda, M. (2007) Secondary abnormalities of neurotransmitters in infants with neurological disorders. Dev. Med. Child Neurol. 49, 740–744.CrossRefGoogle Scholar
  12. 12.
    Goudas, L. C., Carr, D. B., Maszczynska, I., Marchand, J. E., Wurm, W. H., Greenblatt, D. J. (1997) Differential effect of central versus parenteral administration of morphine sulfate on regional concentrations of reduced glutathione in rat brain. Pharmacology 54, 92–97.CrossRefGoogle Scholar
  13. 13.
    Goudas, L. C., Langlade, A., Serrie, A., Matson, W., Milbury, P., Thurel, C. (1999) Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain. Anesth. Analg. 89, 1209–1215.CrossRefGoogle Scholar
  14. 14.
    Gutteridge, M. C., Halliwell, B. (1990) The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem. Sci. 5, 129–135.CrossRefGoogle Scholar
  15. 15.
    Halford, J. C., Harrold, J. A., Boyland, E. J., Lawton, C. L., Blundell, J. E. (2007) Serotonergic drugs: effects on appetite expression and use for the treatment of obesity. Drugs 67, 27–55.CrossRefGoogle Scholar
  16. 16.
    Hampson, A. J., Grimaldi, M., Axelrod, J., Wink, D. (1998) Cannabidiol and (-) D9-tetrahydrocanna-binol are neuroprotective antioxidants. Proc. Natl. Acad Sci. USA. 95, 8268–8273.CrossRefGoogle Scholar
  17. 17.
    Hissin, P. J., Hilf R. (1976) A fiuorometric method for determination of oxidized and reduced glutathione in tissue. Anal. Biochem. 74, 214–226.CrossRefGoogle Scholar
  18. 18.
    Jhamandas, J. H., Harris, K. H., Petrov, T., Jhamandas, K. H. (1996) Activation of nitric oxide-synthesizing neurones during precipitated morphine withdrawal. Neuroreport 7, 2843–2846.CrossRefGoogle Scholar
  19. 19.
    Keromov, B. F. (2004) Glutathione-deficient state of nervous tissues in starved animals intensifies lipid peroxidation and oxidation of protein SH-groups. Ukr Biokhim. Zh 76, 108–113.Google Scholar
  20. 20.
    Lue, W. M., Su, M. T., Lin, W. B., Tao, P. L. (1999) The role of nitric oxide in the development of morphine tolerance in rat hippocampal slices. Eur. J. Pharmacol. 383, 129–135.CrossRefGoogle Scholar
  21. 21.
    Masocha, W., González, L. G., Baeyens, J. M., Agil, A. (2002) Mechanisms involved in morphine-induced activation of synaptosomal Na+, K+-ATPase. Brain Res. 957, 311–319.CrossRefGoogle Scholar
  22. 22.
    Masocha, W., Horvath, G., Agil, A., Ocaña, M., Pozo, E., Szikszay, M. (2003) Role of Na+, K+-ATPase in morphine-induced antinociception. J. Pharmacol. Exp. Ther 306, 1122–1128.CrossRefGoogle Scholar
  23. 23.
    Muñoz, C. J., Montilla, P., Padillo, F. J., Bujalance, I., Muñoz, M. C., Muntané, J. (2006) Role of serotonin in cerebral oxidative stress in rats. Acta Neurobiol. Exp. 66, 1–6.Google Scholar
  24. 24.
    Ossipov, M. H., Lai, J., King, T., Vanderah, T. W., Porreca, F. (2005) Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers 80, 319–324.CrossRefGoogle Scholar
  25. 25.
    Pillai, N. P., Ross, D. H. (1986) Effects of opiates on high-affinity Ca2+, Mg2+-ATPase in brain membrane subfractions. J. Neurochem. 47, 1642–1646.CrossRefGoogle Scholar
  26. 26.
    Puppala, B. L., Matwyshyn, G., Bhalla, S., Gulati, A. (2004) Evidence that morphine tolerance may be regulated by endothelin in the neonatal rat. Biol. Neonate 86, 138–144.CrossRefGoogle Scholar
  27. 27.
    Prunet, M. B., Desbazeille, M., Bros, A., Louche, K., Delagrange, P., Renard, P. (2003) Melatonin reduces body weight gain in sprague dawley rats with diet-induced obesity. Endocrinology 144, 5347–5352.CrossRefGoogle Scholar
  28. 28.
    Sadee, W., Wang, D., Bilsky, E. J. (2005) Basal opioid receptor activity, neutral antagonists, and therapeutic opportunities. Life Sci. 76, 1427–1437.CrossRefGoogle Scholar
  29. 29.
    Sakabe, T., Dahlgren, N., Carlsson, A., Siesjö, B. K. (1982) Effect of diazepam on cerebral monoamine synthesis during hypoxia and hypercapnia in the rat. Physiol. Scand. 115, 57–65.CrossRefGoogle Scholar
  30. 30.
    Saner, A., Pletscher, A. (1979) Effect of diazepam on cerebral 5-hydroxytryptamine synthesis. Eur. J. Pharmacol. 55, 315–318.CrossRefGoogle Scholar
  31. 31.
    Seamon, M. J., Fass, J. A., Maniscalco-Feichtl, M., Abu-Shraie, N. A. (2007) Medical marijuana and the developing role of the pharmacist. Am. J. Health Sys. Pharm. 64, 1037–1044.CrossRefGoogle Scholar
  32. 32.
    Sethi, B. B., Trivedi, J. K., Kumar, P., Gulati, A., Agarwal, A. K., Sethi, N. (1996) Antianxiety effect of cannabis: involvement of central benzodiazepine receptors. Biol. Psychiatry 21, 3–10.CrossRefGoogle Scholar
  33. 33.
    The Statistical Discovery Software SDS, Version 7.0 by SAS Institute Inc, 2003.Google Scholar
  34. 34.
    Sun, Y. (1990) Free radicals, antioxidants enzymes and carcinogenesis. Free Rad Biol. Med. 8, 583–599.CrossRefGoogle Scholar
  35. 35.
    Wan-Kan, O., Hosein, E. A. (1981) Synaptosomal Na+, K+ ATPase as a membrane probe in studying the in vivo action of morphine. Can. J. Biochem. 59, 687–692.CrossRefGoogle Scholar
  36. 36.
    Wall, M. E., Brine, D. R., Perez, R. M. (1976) Metabolism of cannabinoids in man. In: Braude, M. C., Szara, S. (eds) Pharmacol of Marijuana. Raven Press, New York, pp. 93–116.Google Scholar
  37. 37.
    Wickelgren, I. (1997) Marijuana: harder than throught? Science 276, 1967–1968.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest 2010

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), 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.

Authors and Affiliations

  • G. D. Calderón
    • 1
  • Gabriela J. Esquivel
    • 1
  • Ernestina H. García
    • 2
  • Norma B. Osnaya
    • 3
  • H. Juárez Olguín
    • 2
    • 4
    Email author
  1. 1.Laboratorio de NeuroquimicaInstituto Nacional de Pediatría (INP)Mexico
  2. 2.Laboratorio de FarmacologíaINPMexico
  3. 3.Laboratorio de Patología ExperimentalINPMexico
  4. 4.Departamento de Farmacologia, Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoMexico

Personalised recommendations