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The anti-inflammatory prostaglandin 15d-PGJ2 decreases oxidative/nitrosative mediators in brain after acute stress in rats

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Abstract

Rationale

Immobilisation stress is followed by accumulation of oxidative/nitrosative mediators in brain after the release of tumour necrosis factor-alpha (TNFα) and other cytokines, nuclear factor kappa B (NFκB) activation, nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) expression in the brain.

Objectives

This study was conducted to assess if some of the anti-inflammatory products of COX can modify the accumulation of oxidative/nitrosative species seen in brain after stress and to study the mechanisms by which this effect is achieved.

Methods

Young-adult male Wistar rats were subjected to a single session of immobilisation during 6 h.

Results

In stressed animals, brain levels of the anti-inflammatory 15d-PGJ2 increases concomitantly with COX-2 expression. Inhibition of COX-2 with NS-398 prevents stress-induced 15d-PGJ2 increase. Injection of supraphysiological doses of 15d-PGJ2 (80–120 μg/kg) decreases stress-induced increase in NOS-2 activity as well as the stress-induced increase in NO metabolites. On the other hand, 15d-PGJ2 decreases stress-induced malondialdehyde (an indicator of lipid peroxidation) accumulation in cortex and prevents oxidation of the main anti-oxidant glutathione. The mechanisms involved in the anti-oxidative properties of 15d-PGJ2 in stress involve NFκB blockade (by preventing stress-induced IκBα decrease) as well as inhibition of TNFα release in stressed animals. At the doses tested, 15d-PGJ2 decreases COX-2 expression and PGE2 release during stress, suggesting an alternative mechanism for this endogenous compound.

Conclusions

These findings demonstrate a role for this anti-inflammatory pathway in the brain response to stress and open the possibility for preventing accumulation of oxidative/nitrosative species and subsequent brain damage.

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Acknowledgements

This work was supported by the Spanish Ministries of Science and Technology (BMC 2001-1912) and Health (ISCIII 01/0650) (J.C.L.).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Universidad Complutense Madrid, 28040, Madrid, Spain

    Borja García-Bueno, José L. M. Madrigal, Ignacio Lizasoain, María A. Moro, Pedro Lorenzo & Juan C. Leza

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  1. Borja García-Bueno
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  2. José L. M. Madrigal
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  3. Ignacio Lizasoain
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  4. María A. Moro
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  5. Pedro Lorenzo
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  6. Juan C. Leza
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Correspondence to Juan C. Leza.

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García-Bueno, B., Madrigal, J.L.M., Lizasoain, I. et al. The anti-inflammatory prostaglandin 15d-PGJ2 decreases oxidative/nitrosative mediators in brain after acute stress in rats. Psychopharmacology 180, 513–522 (2005). https://doi.org/10.1007/s00213-005-2195-5

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