Neurochemical Research

, Volume 32, Issue 1, pp 19–25 | Cite as

Spinal Morphine Administration Reduces the Fatty Acid Contents in Spinal Cord and Brain by Increasing Oxidative Stress

  • İsmail Özmen
  • Mustafa Nazıroğlu
  • H. Ahmet Alici
  • Fikrettin Şahin
  • Mustafa Cengiz
  • İbrahim Eren
Original Paper

Abstract

It is well known that oxidative stress damages bimolecules such as DNA and lipids. No study is available on the morphine-induced oxidative damage and fatty acids changes in brain and spinal tissues. The aim of this work was to determine the effects of morphine on the concentrations and compositions of fatty acid in spinal cord segments and brain tissues in rabbits as well as lipid peroxidation (LP) and glutathione (GSH) levels in cortex brain.

Twelve New Zealand albino rabbits were used and they were randomly assigned to two groups of 6 rabbits each. First group used as control although morphine administrated to rats in second group. Cortex brain and (cervical, thoracic, lumbar) samples were taken.

The fatty acids between n:18.0 and 21.0 were present in spinal cord sections and n:10 fatty acids in control animals were present in the brain tissues. Compared to n:20.0–24.0 fatty acids in spinal cord sections and 8.0 fatty acids in the brain tissues of drug administered animals. The concentration and composition of the fatty acid methyl esters in spinal cord and brain tissues was decreased by morphine treatments. LP levels in the cortex brain were increased although GSH levels were decreased by the morphine administration.

In conclusion, unsaturated fatty acids contents in brain and spinal cord sections and GSH were reduced by administrating spinal morphine although oxidative stress as LP increased. The inhibition oxidative damage may be a useful strategy for the development of a new protection for morphine administration as well as opiate abuse.

Keywords

Morphine Fatty acids Brain Lipid peroxidation Spinal cord Glutathione 

Abbreviations

BBB

Blood-brain barrier

FAs

Fatty acids

FAMEs

Fatty acid methyl esters

ROS

Reactive oxygen species

GSH

Reduced glutathione

PUPAs

Polyunsaturated fatty acids

HR

Heart rate

Notes

Acknowledgment

The authors thank Ayse Gokce, a technician at Biotechnology Application and Research Center, Erzurum, Turkey.

References

  1. 1.
    Atalay M, Sen CK (1999) Physical exercise and antioxidant defenses in the heart. Ann N Y Acad Sci 874:169–177PubMedCrossRefGoogle Scholar
  2. 2.
    Halliwell B, Gutteridge JMC (1999) Free radicals, other reactive species and disease. In Free Radicals in Biology and Medicine, 3rd ed. Halliwell B, Gutteridge JMC, eds, Oxford University Press, New York, pp 639–645Google Scholar
  3. 3.
    Nazıroğlu M (2006) Effects of physical exercise with a dietary vitamins C and E combination on oxidative stress in muscle, liver and brain of streptozotocin- induced diabetic pregnant rat. Vitamin E: New Research. Ed. MH Braunstain, Nova Science Publishers Inc., NY, USA. pp 69–83Google Scholar
  4. 4.
    Guzman DC, Vazquez IE, Brizuela NO, Alvarez RG, Mejia GB, Garcia EH, Santamaria D, de Apreza MR, Olguin HJ (2006) Assessment of oxidative damage induced by acute doses of morphine sulfate in postnatal and adult rat brain. Neurochem Res 31:549–554PubMedCrossRefGoogle Scholar
  5. 5.
    Xu B, Wang Z, Li G, Li B, Lin H, Zheng R, Zheng Q. (2006) Heroin-administered mice involved in oxidative stress and exogenous antioxidant-alleviated withdrawal syndrome. Basic Clin Pharmacol Toxicol. 99:153–161PubMedCrossRefGoogle Scholar
  6. 6.
    Zhang YT, Zheng QS, Pan J, Zheng RL. (2004) Oxidative damage of biomolecules in mouse liver induced by morphine and protected by antioxidants. Basic Clin Pharmacol Toxicol. 95:53–58PubMedGoogle Scholar
  7. 7.
    Nazıroğlu M, Brandsch C. (2006) Dietary hydrogenated soybean oil affects lipid and vitamin E metabolism in rats. J Nutr Sci Vitaminol (Tokyo). 52:83–88, 2006Google Scholar
  8. 8.
    Yilmaz O, Celik S, Cay M, Naziroglu M. (1997) Protective role of intraperitoneally administrated vitamin E and selenium on the levels of total lipid, total cholesterol, and fatty acid composition of muscle and liver tissues in rats. Cell Biochem 64:233–241CrossRefGoogle Scholar
  9. 9.
    Celik S, Yilmaz O, Asan T, Naziroglu M, Cay M, Aksakal M. (1999) Influence of dietary selenium and vitamin E on the levels of fatty acids in brain and liver tissues of lambs. Cell Biochem Funct 17:115–121PubMedCrossRefGoogle Scholar
  10. 10.
    Sherlock Microbial Identification System (version 4.0), MIS Operating manual, 145 pp, MIDI, Inc, Newark, DE, USAGoogle Scholar
  11. 11.
    Mercandate S. (1999) Problems of long-term spinal opioid treatment in advanced cancer patients. Pain 79:1–13CrossRefGoogle Scholar
  12. 12.
    Wagemans MF, van der Valk P, Spoelder EM, Zuurmond WW, de Lange JJ (1997) Neurohistopathological findings after continuous intrathecal administration of morphine or a morphine/bupivacaine mixture in cancer pain patients. Acta Anaesthesiol Scand 41:1033–1038PubMedCrossRefGoogle Scholar
  13. 13.
    Hodgson PS, Neal JM, Pollock JE, Liu SS (1999) The neurotoxicity of drugs given intrathecally (spinal). Anesth Analg 88:797–809PubMedCrossRefGoogle Scholar
  14. 14.
    Yaksh TL, Noueihed RY, Durant PA (1986) Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and morphine in the rat and cat. Anesthesiology 64:54–66, 1986PubMedCrossRefGoogle Scholar
  15. 15.
    Alici HA, Ozmen I, Cesur M, Sahin F (2003) Effect of the spinal drug tramadol on the fatty acid compositions of rabbit spinal cord and brain. Biol Pharm Bull 26:1403–1406PubMedCrossRefGoogle Scholar
  16. 16.
    Placer ZA, Cushman L, Johnson BC (1966) Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359–364PubMedCrossRefGoogle Scholar
  17. 17.
    Sedlak J, Lindsay RHC (1968) Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann’ s reagent. Anal Biochem 25:192–205PubMedCrossRefGoogle Scholar
  18. 18.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin- Phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  19. 19.
    Di Chiara G, Imperato A. (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA. 85:5274–5278PubMedCrossRefGoogle Scholar
  20. 20.
    Olanow CW, Tatton WG. (1999) Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 22:123–144PubMedCrossRefGoogle Scholar
  21. 21.
    Singhal PC, Pamarthi M, Shah R, Chandra D, Gibbons N (1994) Morphine stimulates superoxide formation by glomerular mesangial cells. Inflammation. 18:293–299PubMedCrossRefGoogle Scholar
  22. 22.
    Di Bello MG, Masini E, Ioannides C, Fomusi Ndisang J, Raspanti S, Bani Sacchi T, Mannaioni PF (1998) Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals. Inflamm Res. 47:122–130PubMedCrossRefGoogle Scholar
  23. 23.
    Goudas LC, Langlade A, Serrie A, Matson W, Milbury P, Thurel C, Sandouk P, Carr DB. (1999). Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain. Anesth Analg. 89:1209–1215PubMedCrossRefGoogle Scholar
  24. 24.
    Farooqui AA, Yi Ong W, Lu XR, Halliwell B, Horrocks LA. (2001) Neurochemical consequences of kainate-induced toxicity in brain: involvement of arachidonic acid release and prevention of toxicity by phospholipase A(2) inhibitors. Brain Res Brain Res Rev 38:61–78PubMedCrossRefGoogle Scholar
  25. 25.
    Kumar R, Agarwal AK, Seth PK (1996) Oxidative stress-mediated neurotoxicity of cadmium. Toxicol Lett 89:65–69PubMedCrossRefGoogle Scholar
  26. 26.
    Subramaniam R, Roediger F, Jordan B, Mattson MP, Keller JN, Waeg G, Butterfield DA (1997) The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the conformation of cortical synaptosomal membrane proteins. J Neurochem 69:1161–1169PubMedCrossRefGoogle Scholar
  27. 27.
    Alici HA, Ozmen I, Cesur M, Sahin F. (2003) Effect of the spinal drug tramadol on the fatty acid compositions of rabbit spinal cord and brain. Biol Pharm Bull 26:1403–1406PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • İsmail Özmen
    • 1
  • Mustafa Nazıroğlu
    • 2
  • H. Ahmet Alici
    • 3
  • Fikrettin Şahin
    • 4
  • Mustafa Cengiz
    • 1
  • İbrahim Eren
    • 5
  1. 1.Department of Chemistry, Art and Science FacultySuleyman Demirel UniversityIspartaTurkey
  2. 2.Department of Biophysics, Faculty of MedicineSuleyman Demirel UniversityIspartaTurkey
  3. 3.Department of Anesthesiology and Reanimation, Medical FacultyAtaturk UniversityErzurumTurkey
  4. 4.Department of Genetic and BioengineeringYeditepe UniversityIstanbulTurkey
  5. 5.Department of Psychiatry, Faculty of MedicineSuleyman Demirel UniversityIspartaTurkey

Personalised recommendations