JOURNAL OF APPLIED TOXICOLOGY J. Appl. Toxicol. 2008; 28: 974–986 Published online 12 June 2008 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/jat.1363 Copyright © 2008 John Wiley & Sons, Ltd. John Wiley & Sons, Ltd. Cadmium-induced neurological disorders: prophylactic role of taurine CADMIUM-INDUCED NEUROLOGICAL DISORDERS Mahua Sinha, Prasenjit Manna and Parames C. Sil* Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata-700009, India Received 28 April 2008; Accepted 30 April 2008 ABSTRACT: The present study was conducted to investigate whether the conditionally essential amino acid taurine could play any protective role against the potent neurotoxin cadmium (Cd)-induced oxidative impairment in mice brain. Cd administration in the form of CdCl 2 (at a dose of 4 mg kg -1 body weight for 3 days, orally) increased the intracellular accumulation of metallic Cd, reactive oxygen species and super oxide radicals. The toxin also augmented the extent of lipid peroxidation, protein carbonylation and the levels of glutathione disul¼de. Activities of the antioxidant enzymes and the levels of reduced glutathione as well as total thiols have been signi¼cantly decreased due to Cd exposure. In addition, the toxin also caused signi¼cant DNA degradation (as evidenced from DNA smearing and diphenylamine reaction). Oral administration of taurine (at a dose of 100 mg kg -1 body weight for 5 days) was found to be very effective in the prevention of Cd-induced oxidative impairment in the brain tissue of experimental mice. In addition, taurine treatment could also prevent the reduction in the in vivo antioxidant power linearly up to a dose of 100 mg kg -1 body weight. The preventive role of taurine against Cd-induced cerebral oxidative damage was supported by the observation under scanning electron microscope as well as histological examination of brain segments. To validate the experimental results, a well-known water soluble antioxidant, vitamin C, was used as the positive control in the study. In all, the results suggest that taurine plays a bene¼cial role against Cd-induced cerebral oxidative stress. Copyright © 2008 John Wiley & Sons, Ltd. KEY WORDS: Cadmium; neuro toxin; cerebral oxidative stress; taurine; antioxidant; neuro protection Introduction Cadmium (Cd) is a cumulative heavy metal poison and does not play any constructive role in the human body. It is a noxious agent and has a very long biological half-life (Arabi and Mohammadpour, 2006). Along with its com- pounds, it is extremely toxic even in low concentrations, and will bioaccumulate in organisms and ecosystems. Beside occupational exposure, it enters the body through food and drinking water as well as through inhalation. As it targets ubiquitous enzyme reactions, it affects nearly all organ systems (WHO 1992; US Department of Health and Human Services 1997). In animals, the brain is the most complex organ, enclosed within the skull and continuous with the spinal cord. It is the part of central nervous system, which includes all the higher nervous centers. The blood–brain barrier (BBB) gives protection to the brain from harmful chemicals and only allows the entrance of essential nutrients. Normally it is dif¼cult for any foreign compound, like Cd, to cross the BBB. But during the developmental stage, when this barrier is not fully matured, Cd can enter the brain, accumulate in dif- ferent regions, initiate lipid peroxidation and weaken the antioxidant defense (Gabbiani et al., 1967; Manca et al., 1991; Gutierrez-Reyes et al., 1998). Cd is known to cause disorder in the central nervous system (Gulati et al., 1987; Tacey et al., 1990). The mechanism through which Cd produces neurotoxicity remains to be elucidated. Cd exposure generates a large amount of reactive oxygen species (ROS) that can impair the cellular antioxidant defense system and simultaneously damage cellular ingredients such as lipids, proteins and DNA (Casalino et al., 2002). The brain is highly susceptible to oxidative damage because of its poor antioxidant defense system (Mates, 2000). Oxidative stress may, therefore, be one of the reasons for Cd-induced brain dysfunction. In this connection, attention has been focused on com- pounds having antioxidant properties. Many investigators have considered taurine as a potent antioxidant (Huxtable, 1992; Son et al., 2007); it is present in the most animal tissues and is particularly abundant in aquatic foods. In nature it plays major role as a substrate in the conjugation of bile acids in the liver (Flora et al., 2004). It is abun- dant in human breast milk and is thought to be important in infant brain and retinal development. Taurine might protect cell membrane from toxic substances, detoxify harmful substances and modulate cellular calcium ½ux and neuronal excitability (Wessberg et al., 1983; Huxtable, 1992; Hwang and Wang, 2001). It may be considered as a direct antioxidant due to its ability to scavenge ROS * Correspondence to: P. C. Sil, Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata-700009, India. E-mail: parames@bosemain.boseinst.ac.in