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Oxidative Medicine and Cellular Longevity
Volume 2013 (2013), Article ID 264935, 10 pages
http://dx.doi.org/10.1155/2013/264935
Research Article

Oxidative Stress Is Related to the Deleterious Effects of Heme Oxygenase-1 in an In Vivo Neuroinflammatory Rat Model

1UMR INSERM U930, Université François Rabelais de Tours, PRES Centre Val de Loire Université, 37000 Tours, France
2EA 4708, IPROS, CHR Orléans, BP 2439, 1 rue Porte Madeleine, 45032 Orléans, France
3Département Pharmacie, CHRU de Tours, Tours, France

Received 5 November 2012; Revised 21 January 2013; Accepted 22 January 2013

Academic Editor: Sumitra Miriyala

Copyright © 2013 Claire Tronel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Heme oxygenase-1 (HO-1) induction is associated with beneficial or deleterious effects depending on the experimental conditions adopted and the neurodegenerative rodent models used. The present study aimed first to evaluate the effects of cerebral HO-1 induction in an in vivo rat model of neuroinflammation by intrastriatal injection of quinolinic acid (QA) and secondly to explore the role played by reactive oxygen species (ROS) and free iron (Fe2+) derived from heme catabolism promoted by HO-1. Chronic I.P. treatment with the HO-1 inductor and substrate hemin was responsible for a significant dose-related increase of cerebral HO-1 production. Brain tissue loss, microglial activation, and neuronal death were significantly higher in rats receiving QA plus hemin (H-QA) versus QA and controls. Significant increase of ROS production in H-QA rat brain was inhibited by the specific HO-1 inhibitor ZnPP which supports the idea that ROS level augmentation in hemin-treated animals is a direct consequence of HO-1 induction. The cerebral tissue loss and ROS level in hemin-treated rats receiving the iron chelator deferoxamine were significantly decreased, demonstrating the involvement of Fe2+in brain ROS production. Therefore, the deleterious effects of HO-1 expression in this in vivo neuroinflammatory model were linked to a hyperproduction of ROS, itself promoted by free iron liberation.