Brain Injury, December 2009; 23(13–14): 1089–1094 Protective effect of resveratrol against lipopolysaccharide-induced oxidative stress in rat brain HICHEM SEBAI 1,2 , WAFA GADACHA 1 , MAMANE SANI 1 , EZZEDINE AOUANI 3 , NE ´ ZIHA GHANEM-BOUGHANMI 3 , & MOSSADOK BEN-ATTIA 1 1 Laboratoire de Biosurveillance de l’Environnement, Faculte ´ des Sciences de Bizerte, 7021 Zarzouna, Tunisie, 2 INSERM UMR-911 CRO2, Aix-Marseille Universite ´, Faculte ´ de Me ´decine-Timone, 27 Bld Jean Moulin, 13385 Marseille cedex 05, France, and 3 Laboratoire des Substances Biologiquement Actives, Centre de Biotechnologie, Technopole Borj-Cedria, BP-901, 2050 Hammam-lif, Tunisia (Received 5 December 2008; revised 19 September 2009; accepted 29 September 2009) Abstract Primary objective: To study the protective effect of resveratrol on endotoxemia-induced neurotoxicity. Methods: Rats were pre-treated during 7 days with 20 mg kg 1 body weight (b.w.) resveratrol and challenged with a single dose of lipopolysaccharide (LPS: 8 mg kg 1 b.w.) for 24 hours. Brains were harvested to determine LPS-induced lipoperoxidation level, antioxidant enzyme activities, nitric monoxide (NO) and iron distribution as well as the impact of resveratrol on these parameters. Results: Resveratrol counteracted LPS-induced brain malondialdehyde (MDA) level and antioxidant enzyme activities depletion as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Resveratrol also reversed LPS-induced brain and plasma NO elevation as well as iron sequestration from plasma to brain compartment. Conclusion: The data suggest that resveratrol is capable of alleviating LPS-induced neurotoxicity by a mechanism that may involve iron shuttling proteins. Keywords: Resveratrol, lipopolysaccharide, neuroprotection, oxidative stress, nitric oxide, iron Abbreviations: BHT, Butylated hydroxytoluene; CAT, Catalase; LPS, Lipopolysaccharide; MDA, Malondialdehyde; NO, Nitric oxide; NOS,Nitric oxide synthase; POD, Peroxidase; ROS,Reactive oxygen species; RVT, Resveratrol; SOD, Superoxide dismutase; TBA, Thiobarbituric acid; TCA, Trichloroacetic acid Introduction Lipopolysaccharide (LPS) is a major component of the cell wall of gram negative bacteria contributing to the pathogenesis of bacterial infection. This endotoxin has harmful effects on various organs [1] including the brain, partly through the induction of inflammatory mediators [2], which in turn could lead to an oxidative stress status. This latter is characterized by depletion from intracellular stores of endogenous antioxidants or by rapid alteration of antioxidant enzymes as SOD, CAT and POD, resulting in increased lipoperoxidation [3]. The brain is particularly sensitive to oxidative damage because it is a high energy expenditure organ, rich in polyunsaturated fatty acids, a main target of lipid peroxidation [4]. Resveratrol (trans-3,5,4 0 trihydrox- ystilbene), a polyphenolic phytoalexin abundantly found in grapes and red wine, deserves a lively interest in biomedical research. In vivo, resveratrol exhibits protective properties on kidney [5], heart [6] and brain [7]. In vitro, this polyphenol which inhibits cellular events associated with tumour initiation, Correspondence: Mossadok Ben-Attia, Laboratoire de Biosurveillance de l’Environnement (LBE), De ´partement des Sciences de la Vie, Faculte ´ des Sciences de Bizerte, 7021 Zarzouna, Tunisia. Fax: þ(216) 72 590 566. E-mail: benattia.mossa@gmail.com ISSN 0269–9052 print/ISSN 1362–301X online ß 2009 Informa Healthcare Ltd. DOI: 10.3109/02699050903379370