Central administration of corticotropin-releasing factor induces tissue specific oxidative damage in chicks Ahmad Mujahid ⁎, Mitsuhiro Furuse Laboratory of Advanced Animal and Marine Bioresources, Faculty of Agriculture, Kyushu University, 6-10-1, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan abstract article info Article history: Received 20 July 2008 Received in revised form 12 August 2008 Accepted 13 August 2008 Available online 22 August 2008 Keywords: CRF Intracerebroventricular Oxidative damage MDA Neonatal chick Corticotropin-releasing factor (CRF) modulates the activity of the hypothalamic–pituitary–adrenal (HPA) axis, and has a key role in mediating neuroendocrine effects which occur in response to stressful stimuli. We have recently shown that intracerebroventricular (ICV) injection of CRF in neonatal chicks increased homeothermy that was associated with enhanced gene transcripts of mitochondrial fatty acid (FA) transport and oxidation enzymes in a tissue specific manner. These observations prompted an investigation into the potential role of CRF in a state of oxidative damage in different tissues. We therefore, investigated whether CRF-induced changes in metabolism are accompanied by oxidative damage in the plasma, brain and other tissues. Neonatal chicks (Gallus gallus) with or without ICV-CRF (42 pmol) were kept at thermoneutral temperature (30 °C). After 3 h, malondialdehyde (MDA) was measured in the plasma, brain, heart, liver and skeletal muscle (gastrocnemius). ICV-CRF significantly decreased the weight gain and feed consumption of chicks. Plasma, heart and liver revealed significantly higher MDA levels in chicks with ICV-CRF as compared to that of control chicks, but this pattern was not observed in the brain and muscle. Gene transcripts of enzymes involved in mitochondrial FA transport and oxidation, and 3-hydroxyacyl CoA dehydrogenase and citrate synthase enzyme activities in the brain were not changed by ICV-CRF. In conclusion, central administration of CRF in neonatal chicks induces tissue specific oxidative damage: higher MDA levels were observed in the heart and liver while no such change occurred in the brain and muscle. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Regulation of energy homeostasis is an important function of the central nervous system (CNS) requiring adaptive responses to maintain and support life. Many central factors influence this regulation that is vital for habituation, thermogenesis, and metabolism. A major upstream determinate of these responses is corticotropin-releasing factor (CRF), a 41-amino acid peptide hormone produced in the hypothalamus. CRF has multiple biological effects and plays a central regulatory role in the hypothalamic–pituitary–adrenal (HPA) axis. CRF rapidly mobilizes the organism in response to stressors and also stimulates the CNS to respond to environmental challenges. The CRF family of peptides is capable of strong anorectic and thermogenic effects, and plays a role in the regulation of energy balance (Richard et al., 2002). In mammals, central administration of CRF elevates sympathetic outflow (Brown et al., 1982a), sympathetic nerve activity to brown adipose tissue (Egawa et al., 1990), catecholamines (Brown et al., 1982a; Dunn and Berridge, 1987), and corticosterone (Brown et al., 1982b). Additionally, intracerebroventricular (ICV) infusion of urocor- tin (member of CRF family) or CRF increases whole body O 2 consumption and colonic temperature (de Fanti and Martinez, 2002). In neonatal chicks, CRF has been reported to activate HPA responses (Furuse et al., 1997). The activation of the HPA axis plays a role in thermogenesis of neonatal chicks: central administration of CRF- induced hyperthermia (Tachibana et al., 2004; Mujahid and Furuse, 2008a), and dose-dependently increased O 2 consumption, CO 2 and heat production (Tachibana et al., 2006). We have recently shown that ICV-CRF induces hyperthermia in neonatal chicks and increases the gene transcripts of enzymes involved in mitochondrial FA transport and oxidation, and subsequently the FA oxidation enzyme activities in a tissue specific manner along with higher levels of plasma NEFA (Mujahid and Furuse, 2008a). Thus, the CRF-induced increased expression and activity of mitochondrial FA transport and oxidation enzymes, and associated hyperthermia may expose the tissues to oxidative stress: hyperthermia and increased expression of mitochon- drial FA transport and oxidation enzymes were observed in heat- stressed chickens with enhanced reactive oxygen species production and oxidative damage (Mujahid et al., 2005, 2006, 2007a,b). The ICV route of administration is used commonly to assess central effects of neuropeptides. To our knowledge, the effect of ICV-CRF to exert Comparative Biochemistry and Physiology, Part A 151 (2008) 664–669 Abbreviations: 3HADH, 3-hydroxyacyl CoA dehydrogenase; AD, Alzheimer's disease; CNS, central nervous system; CPT-I, carnitine-palmitoyl-transferase-I; CPT-II, carnitine- palmitoyl-transferase-II; CS, citrate synthase; CRF, corticotropin-releasing factor; EB, evans blue; FA, fatty acid; HPA, hypothalamic–pituitary–adrenal; ICV, intracerebroventricular; LCAD, long-chain acyl CoA dehydrogenase; MDA, malondialdehyde; NEFA, non-esterified fatty acid; TBARS, thiobarbituric acid reactive substances; ROS, reactive oxygen species. ⁎ Corresponding author. Tel./fax: +81 92 642 2953. E-mail address: ahmad@brs.kyushu-u.ac.jp (A. Mujahid). 1095-6433/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.cbpa.2008.08.013 Contents lists available at ScienceDirect Comparative Biochemistry and Physiology, Part A journal homepage: www.elsevier.com/locate/cbpa