International Journal of Pharmaceutical Science Invention ISSN (Online): 2319 – 6718, ISSN (Print): 2319 – 670X www.ijpsi.org Volume 5 Issue 2 ‖ April 2016 ‖ PP.05-13 www.ijpsi.org 5 | P a g e Protective Effects of Alpha Lipoic Acid (α -LA) Against Lead Neuro-Toxicity in albino Rats Dr. Eman Mohammed Mohammed Abd-Ella 1 , Prof. Suzan Fahmy El-Sisy 3 , Heba Ahmed Abd El-Hamed El-Dash 3 1 Lecturer of Histology and Histochemistry, zoology department, Faculty of Science, Fayoum University 2 Professor: Zoological Physiology, Branch of Zoology, National Organization of Drugs Control and Research, Giza. 3 Assistant lecturer at Zoology Department, Faculty of Science, Fayoum University ABSTRACT Aim of the work: The present study was conducted to elucidate the possible protective effect of alpha lipoic acid (α-LA) against the deleterious effect perturbation induced in rat brain exposed to lead acetate. Methods: 32 Wistar male rats (weighing 130 ± 10 g) were divided into four groups (n=8): (1) normal control group (C); (2) Initiation group (Pb as lead acetate 20 mg/kg.b.wt, i.p. for 2 wks); (3) treatment group (α-LA 20 mg/kg.b.wt, i.p. for 3 wks); (4) post-initiation treatment group (Pb for 2 wks then followed by α-LA for 3 wks). Levels of monoamines (norepinephrine NE and dopamine DA), the level of Ache activity and finally adenosine triphosphate (ATP), were estimated in the hippocampus and cerebral cortex, in addition, a Morris water maze and the histological study were performed after completion of the experiments. Results: The results of the present work demonstrated that Pb inhibited neurotransmitters releases and decrease the level of Ache activity, as well as it inhibited energy production ATP. Pb impaired performance on Morris Water Maze of rats and histological degeneration. However, treatment with α-LA significantly attenuated the behavioral impairment and biochemical parameters in rat treated with Pb. And amelioration of histological changes. Conclusion: As a conclusion, treatment with α-LA can improve the Pb-induced toxicity via antioxidant activity. KEYWORDS: neurotoxicity; alpha lipoic acid; histopathology; lead toxicity; and animal behavior I. NTRODUCTION Lead (plumbum, Pb 2+ ) is a pervasive and persistent environmental toxic metal. Despite considerable efforts to identify and eliminate sources of Pb 2+ exposure, this metal remains induces adverse health effects for centuries (Khodamoradi et al., 2015). Pb 2+ had modest uses in ancient medicines. Today, it used in many products including alkyl-lead petroleum combustion, production, and storage of lead-acid batteries, leaded glass, cement manufacture, production of plastics & ceramics and also found in some imported cosmetics (Karamian et al., 2015). Pb exposure occurs mainly via food, water or air and soil ( Khodamoradi et al., 2015). Pb 2+ can damage various body systems, however, the central nervous system is the primary target (Karamian et al., 2015 and Li et al., 2016). Several reports have demonstrated that exposure to lead causes deleterious effects on the nervous system, including decrements in IQ, impaired cognition, and memory, as well as impaired peripheral nerve functions and related behavioral disturbances ( Khodamoradi et al., 2015). Moreover, Pb 2+ can pass through the blood–brain barrier due to its ability to substitute for calcium ions, so it induces damage in the prefrontal cerebral cortex, hippocampus, and cerebellum then leading to a variety of neurological disorders, such as mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, schizophrenia and Parkinson's disease (Bazrgar, Goudarzi, Lashkarbolouki et al., 2015). Oxidative stress by disrupting the pro-/antioxidant balance in the cells (Bokara et al., 2008), deregulation of cell signaling, and neurotransmission impairment are regarded as key involved in lead neurotoxicity (Li et al., 2016). Antioxidants play a major role in the treatment of Pb poisoning. Lipoic acid (LA), thioctic acid, or 1, 2 dithiole-3-pentanoic acids, is a natural organosulfur compound that synthesized in mitochondria from its precursors cysteine and octanoic acid (Bilska and Wlodek, 2005), which is an essential cofactor for certain dehydrogenase enzymes during mitochondrial energy metabolism. It is found in various types of food such as kidney, liver, heart, yeast extract, broccoli, and spinach. Exogenous lipoic acid is available in the form of synthetic food supplements (Sitton et al., 2004). It is reduced to its biologically active form dihydrolipoic acid (DHLA) in the CNS and almost all other tissues. Additionally, it acts as a potent antioxidant role in the CNS through it able to cross the blood–brain barrier and on its equal uptake by the central and the peripheral nervous