Skip to main content
Log in

Fish oil, melatonin and vitamin E attenuates midbrain cyclooxygenase-2 activity and oxidative stress after the administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine

  • Original Paper
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Parkinson’s disease is a neurodegenerative disease whose hallmark pathological features include a selective loss of dopaminergic neurons in the midbrain. Ciclooxygenase-2 activity induction and oxidative stress have been implicated in the aetiology of Parkinson’s disease and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Upon administration of fish oil, melatonin and vitamin E, neuroprotective effects on MPTP-induced neurotoxicity have been indicated. The aim of this study was to investigate the time course and compare the potency of these agents alone, on several parameters such as COX-2 and lipid peroxides (LPO) products associated with MPTP neurotoxicity in midbrain homogenates of C57BL/6 mice. Using fish oil (0.0368 g EPA and 0.0184 g DHA, per day), melatonin (10 mg/kg/day), and vitamin E (50 mg/Kg/day) we have now shown that COX-2 activity, LPO and nitrite/nitrate levels were significantly increased in MPTP treated mice (p < 0.001) while fish oil, melatonin and vitamin E treatment were capable of decreasing significantly the outcome of all above noted parameters (p < 0.05). The effect of fish oil on COX-2 activity and nitrite/nitrate levels was more profound than that of vitamin E or melatonin while the latter was more effective on reducing the LPO levels compared to fish oil and vitamin E. In conclusion, the outcome of the neuroprotective effects of these agents is long lasting and of variable potency indicating a different anti-inflammatory mode of action.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Akbar M, Calderon F, Wen Z, Kim HY (2005) Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci USA 102:10858–10863

    Article  PubMed  CAS  Google Scholar 

  • Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology 35:949–956

    Article  PubMed  CAS  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of proteins utilizing the principle of protein-dye binding. Analyt Biochem 72:248–256

    Article  PubMed  CAS  Google Scholar 

  • Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83(6 Suppl):1505S–1519S

    PubMed  CAS  Google Scholar 

  • Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O et al (2004) Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron 43:633–645

    Article  PubMed  CAS  Google Scholar 

  • Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N Jr et al (2005) Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer’s disease. Eur J Neurosci 22:617–626

    Article  PubMed  Google Scholar 

  • de Rijk MC, Breteler MM, den Breeijen JH, Launer LJ, Grobbee DE, van der Meché FG et al (1997) Dietary antioxidants and Parkinson disease. The Rotterdam Study. Arch Neurol 54:762–765

    Article  PubMed  Google Scholar 

  • Dieber-Rotheneder M, Puhl H, Waeg G, Striegl G, Esterbauer H (1991) Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res 32:1325–1332

    PubMed  CAS  Google Scholar 

  • Eling TE, Glasgow WC, Curtis JF, Hubbard WC, Handler JA (1991) Studies on the reduction of endogenously generated prostaglandin G2 by prostaglandin H synthase. J Biol Chem 266:12348–12355

    PubMed  CAS  Google Scholar 

  • Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products malonaldehyde and 4-hydroxynonenal. Meth Enzymol 186:407–421

    Article  PubMed  CAS  Google Scholar 

  • Feng Z, Li D, Fung PC, Pei Z, Ramsden DB, Ho SL (2003) COX-2-deficient mice are less prone to MPTP-neurotoxicity than wild-type mice. Neuroreport 14:1927–1929

    Article  PubMed  CAS  Google Scholar 

  • Galano A, Tan DX, Reiter RJ (2011) Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 51:1–16

    Article  PubMed  CAS  Google Scholar 

  • Galano A, Tan DX, Reiter RJ (2013) On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J Pineal Res 54:245–257

    Article  PubMed  CAS  Google Scholar 

  • Ghasemi A, Hedayati M, Biabani H (2007) Protein precipitation methods evaluated for determination of serum nitric oxide end products by the Greiss Assay. J Med Sci Res 2:29–32

    Google Scholar 

  • Hashimoto M, Hossain S, Shimada T, Sugioka K, Yamasaki H, Fujii Y et al (2002) Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer’s disease model rats. J Neurochem 81:1084–1091

    Article  PubMed  CAS  Google Scholar 

  • Jackson-Lewis V, Smeyne RJ (2005) MPTP and SNpc DA neuronal vulnerability: role of dopamine, superoxide and nitric oxide in neurotoxicity. Neurotox Res 7:193–202

    Article  PubMed  CAS  Google Scholar 

  • Liberatore G, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WJ et al (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Nat Med 5:1403–1409

    Article  PubMed  CAS  Google Scholar 

  • Maclean CH, Issa AM, Newberry SJ, Mojica WA, Morton SC, Garland RH et al (2005) Effects of omega-3 fatty acids on cognitive function with aging, dementia, and neurological diseases. Evid Rep Technol Assess (Summ) 113:1–4

    Google Scholar 

  • Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I et al (2006) Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis 23:563–572

    Article  PubMed  CAS  Google Scholar 

  • Ortiz GG, Crespo-López ME, Morán-Moguel C, García JJ, Reiter RJ, Acuña-Castroviejo D (2001) Protective role of melatonin against MPTP-induced mouse brain cell DNA fragmentation and apoptosis in vivo. Neuro Endocrinol Lett 22:101–108

    PubMed  CAS  Google Scholar 

  • Reiter RJ (2003) Melatonin: clinical relevance. Best Pract Res Clin Endocrinol Metab 17:273–285

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez C, Mayo JC, Sainz RM, Antolín I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9

    Article  PubMed  CAS  Google Scholar 

  • Salem N Jr, Litman B, Kim HY, Gawrisch K (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 36:945–959

    Article  PubMed  CAS  Google Scholar 

  • Sanchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell AL, Isacson O (2004) Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation 1:6

    Article  PubMed  Google Scholar 

  • Schulz JB, Falkenburger BH (2004) Neuronal pathology in Parkinson’s disease. Cell Tissue Res 318:135–147

    Article  PubMed  Google Scholar 

  • Smith WL, Marnett LJ, DeWitt DL (1991) Prostaglandin and thromboxane biosynthesis. Pharmacol Ther 49:153–179

    Article  PubMed  CAS  Google Scholar 

  • Tan DX, Chen LD, Poeggeler B, Manchester LC, Reiter RJ (1993) Melatonin : a potent, endogenous hydroxyl radical scavenger. Endocr J 1:57–60

    Google Scholar 

  • Teismann P, Tieu K, Choi DK et al (2003) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA 100:5473–5478

    Article  PubMed  CAS  Google Scholar 

  • Wu A, Ying Z, Gomez-Pinilla F (2004) Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 21:1457–1467

    Article  PubMed  Google Scholar 

  • Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C et al (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22:1763–1771

    PubMed  CAS  Google Scholar 

  • Yeleswaram K, McLaughlin LG, Knipe JO, Schabdach D (1997) Pharmacokinetics and oral bioavailability of exogenous melatonin in preclinical animal models and clinical implications. J Pineal Res 22:45–51

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are indebted to Dr Gustavo Orozco-Aviña from ZONE/DIET for a generous supply of fish oil.

Competing interests

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fermín P. Pacheco-Moisés.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortiz, G.G., Pacheco-Moisés, F.P., Gómez-Rodríguez, V.M. et al. Fish oil, melatonin and vitamin E attenuates midbrain cyclooxygenase-2 activity and oxidative stress after the administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine. Metab Brain Dis 28, 705–709 (2013). https://doi.org/10.1007/s11011-013-9416-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-013-9416-0

Keywords

Navigation