Oxidative stress modulates membrane bound ATPases in brain regions of PCB (Aroclor 1254) exposed rats: Protective role of α-tocopherol

Abstract

Polychlorinated biphenyls (PCBs) are a class of widely dispersed and environmentally persistent organic compounds. PCBs exhibit a wide range of toxicological effects including neurotoxicity. Vitamin E (α-tocopherol) is an important lipid soluble antioxidant placed in a special region of membranes. Large amounts of energy are required to maintain the signaling activities of the cells in the central nervous system (CNS). Membrane proteins that control ion gradients across organellar and plasma membranes appear to be particularly susceptible to oxidation-induced changes. The aim of this study was to determine the protective role of vitamin E on Aroclor 1254 induced modulation in membrane bound ATPases in brain regions of rats. One group of rats received corn oil as vehicle for 30 days as control. The other group of rats were administered Aroclor 1254 at a dose of 2 mg kg⁻¹ bw day⁻¹ intraperitoneally for 30 days. One group of rats received vitamin E (50 mg kg⁻¹ bw day⁻¹) orally simultaneously with Aroclor 1254 for 30 days. After 30 days, the animals were euthanized and the brain was dissected to hypothalamus and hippocampus to determine the following parameters. Hydrogen peroxide (H₂O₂), Lipid peroxidation (LPO) and the activities of Na⁺K⁺-ATPase, Ca²⁺-ATPase and Mg²⁺-ATPase were determined. Reduced glutathione (GSH) level was also determined. Activities of all the enzymes were decreased while an increase in H₂O₂ and LPO were observed in selected brain regions of PCB treated animals. Simultaneous vitamin E treatment in PCB exposed animals restored all the parameters significantly. These results suggest that oxidative stress is involved in the inhibitory effect of PCB (Aroclor 1254) on membrane bound ATPases in selected brain regions. α-tocopherol acts against PCB induced neurotoxicity by decreasing oxidative stress.

Introduction

Numerous toxic substances that are found in the urban environment cause abnormalities in normal growth and development because they persist for many years and can bioaccumulate [1]. Important examples of such toxicants are polychlorinated biphenyls (PCBs) which are widely used in electrical industries, as coolants for transformers and capacitors [2].

Aroclor 1254 is a commercial mixture of PCBs, which is defined as being 54% chlorine by weight [3]. PCBs affect several organ systems in mature and developing animals [4]. The central nervous system is one of the target organs for polychlorinated biphenyls (PCBs). Developmental exposure to PCB mixtures or congeners altered motor activity, neurological development and cognitive function in laboratory animals [5]. The hippocampus has long been implicated in memory function in humans and other animals [6]. In vitro studies have demonstrated perturbations in synaptic transmission and plasticity in hippocampus following acute exposure to some PCB mixtures and specific PCB congeners [7]. Hypothalamus is a part of diencephalon and the nerve cells of hypothalamic nuclei producing the releasing factors or inhibiting factors control the hormone production of the anterior lobe of the hypophysis [8]. Kester et al. [9] showed that PCBs are endocrine disrupting chemicals. Recent studies in our laboratory also suggest that Aroclor 1254 alters male reproductive function by modulating the level of serum sex hormones and their receptors concentration in prostate gland [10], [11].

Oxidative stress is closely involved in several diseases of nervous system including neurodegenerative diseases such as Alzheimer's disease, Parkinson disease and schizophrenia [12]. The brain is particularly sensitive to oxidative damage because of its high levels of unsaturated lipids, as well as a high rate of oxidative metabolism [13]. ROS (Oxy radicals) are generated continuously in nervous system during normal metabolism and neuronal activity [14]. PCB induced toxic manifestations may be associated with the production of free radicals [15].

Neurons require a great amount of ATP to maintain membrane polarization, Ca²⁺ influx from organelles, processing of neurotransmitters, intracellular signaling systems, and axonal and dendritic transport. ATPases are lipid dependent membrane-bound enzymes. Any alteration in the membrane lipid environment alters the ATPase activity and normal cellular functions [16]. Any perturbation in the activities of ATPases affects membrane status by inflicting changes in electrophysiological energetics and normal homeostasis [17]. Na⁺K⁺-ATPase is responsible for the generation of the membrane potential through the active transport of sodium and potassium ions in the CNS necessary to maintain neuronal excitability. Na⁺K⁺-ATPase is present at high concentrations in brain, consuming about 40–50% of the ATP generated in this organ [18]. Ca²⁺-ATPase is responsible for fine tuning of intracellular calcium levels [19]. Moreover, the role of Mg²⁺-ATPase is to maintain high brain intracellular Mg²⁺, changes of which can control rates of protein synthesis and cell growth [20]. Free radicals oxidize polyunsaturated fatty acids (PUFAs), a main component of the membrane, thereby destroying the special arrangement of the membrane and removing biological activities. As a result, the functions of the membrane deteriorate and fluidity decreases, impairing the crucial membrane functions of transport and permeability and also hindering homeostasis [21]. Recent studies showed that the importance of antioxidants such as vitamins protecting the living organism against toxic effects of environmental chemicals. α-tocopherol is the primary liposoluble antioxidant, which may have an important role in scavenging free oxygen radicals and in stabilizing the cell membranes, thus maintaining its permeability [22].

Therefore, the present study was carried out to investigate: (1) the role of oxidative stress on activities of membrane bound ATPases in selected brain regions of Aroclor 1254 exposed male albino rats; (2) the protective role of α-tocopherol in alleviating the negative effects of Aroclor 1254 in the brain regions.