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European Journal of Pharmacology
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Flavonoid quercetin protects against swimming stress-induced changes in oxidative biomarkers in the hypothalamus of rats
Nagaraja Haleagraharaa,⁎, Ammu Radhakrishnan b, Nagarajah Lee c, Ponnusamy Kumar a
a b c
Division of Human Biology, Faculty of Medicine and Health, International Medical University, Kuala Lumpur, 57000, Malaysia Department of Pathology, Faculty of Medicine and Health, International Medical University, Kuala Lumpur, 57000, Malaysia Department of Community Medicine, Faculty of Medicine and Health, International MedicalUniversity, Kuala Lumpur, 57000, Malaysia
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Quercetin is a bioﬂavonoid abundant in onions, apples, tea and red wine and one of the most studied ﬂavonoids. Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. The objective of this study was to investigate the effectof quercetin on stress-induced changes in oxidative biomarkers in the hypothalamus of rats. Adult male Sprague Dawley rats were subjected to forced swimming stress for 45 min daily for 14 days. Effect of quercetin at three different doses (10, 20 and 30 mg/ kg body weight) on serum corticosterone and oxidative biomarkers (lipid hydroperoxides, antioxidant enzymes and total antioxidants) wasestimated. Swimming stress signiﬁcantly increased the serum corticosterone and lipid hydroperoxide levels. A signiﬁcant decrease in total antioxidant levels and super oxide dismutase, glutathione peroxidase and catalase levels was seen in the hypothalamus after stress and treatment with quercetin signiﬁcantly increased these oxidative parameters and there was a signiﬁcant decrease in lipid hydroperoxidelevels. These data demonstrate that forced swimming stress produced a severe oxidative damage in the hypothalamus and treatment with quercetin markedly attenuated these stress-induced changes. Antioxidant action of quercetin may be beneﬁcial for the prevention and treatment of stress-induced oxidative damage in the brain. © 2009 Elsevier B.V. All rights reserved.
Article history: Received 31January 2009 Received in revised form 14 August 2009 Accepted 25 August 2009 Available online 8 September 2009 Keywords: Stress Quercetin Oxidative stress Antioxidant Hypothalamus
1. Introduction Stress is any internal or external stimulus that disturbs the physiological homeostasis and it elicits neurobehavioral alterations (Chakraborti et al., 2007). The central nervous system plays animportant role in the regulation of stress responses and complex neurochemical pathways are involved in the activation of these processes (Carrasco and VandeKar, 2003). Stressors activate sympatho-adrenomedullary system and hypothalamic-pituitary-adrenal (HPA) axis (Cohen and Hamrick, 2003). The hypothalamus is the primary locus for integration of the stress signals originating from different parts of thebody. Reactive oxygen species are generated by a variety of physiological and pathological conditions and despite their vital importance to normal cell function including proliferation, growth, signaling and apoptosis (Reid, 1997) they cause continuous damage to lipids, proteins and DNA (Goto and Nakamura, 1997). Intense stress response results in the release of reactive oxygen species, whichcause lipid peroxidation and play an important role in tissue injury (Saito et al., 2005). Brain is the target for different stressors because of its high
⁎ Corresponding author. Human Biology Division, Faculty of Medicine and Health, International Medical University, Kuala Lumpur, 57000, Malaysia. Tel.: +60 3 27317231, +60 176103431; fax: +60 3 86567229. E-mail address: firstname.lastname@example.org...