International Journal of Bioassays 6.9 (2017) pp. 5474-5484 *Corresponding Author: Dr. Basant Mahmoud Morsy, Chemistry Department, Bio Chemistry Division, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. E-mail: basantmahmoud@yahoo.com DOI: http://dx.doi.org/10.21746/ijbio.2017.9.2 pg. 5474 Research Article The protective effect of Nigella sativa oil extract against neurotoxicity induced by Valproic acid Basant M. Morsy 1 , Ghada Mohamed Safwat 2 , Doaa Ahmed Hussein 1 , Reem Mohamed Samy 3 1 Chemistry Department, Bio Chemistry Division, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. 2 Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University Beni-Suef, Egypt. 3 Biochemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Received: 8/1/2017; Revised: 8/13/2017; Accepted: 8/23/2017 Available online: 1 st September 2017 Abstract: Nigella sativa (NS), commonly known as black cumin, has been used for medicinal purposes. Traditionally the seeds and its oil are used in several diseases. The greatest part of the remedial properties of this plant is due to the presence of thymoquinone (TQ) which is a major active chemical component of the essential oil. The current study performed to evaluate the effect of Nigella sativa oil (NSO) extract on the neurotoxic and hepatotoxic potentials from valproic acid (VPA) administration. Also we summarize recent findings emphasizing the role of main neurotoxic and hepatotoxic markers and oxidative stress in study’s case. Neurotoxicity was induced by VPA at dose of (500 mg/kg b.wt) by gastric intubation daily for 30 day. These rats received NSO extract was given orally at dose of (0.5 ml/kg b.wt) daily for 30 days after VPA administration. The current results revealed that NSO extract treatment ameliorated significantly the elevated levels of the neurotoxic and hepatotoxic biomarkers which elevated as a result to VPA administration. Moreover, NSO extract treatment ameliorated the enzymatic antioxidant, brain and liver catalase (CAT) activity and the non-enzymatic antioxidant, brain and liver glutathione (GSH) and lipid peroxidation (LPO) concentrations. Keywords: Neurotoxicity, Nigella sativa (NS), Valproic acid (VPA). Introduction Neurotoxicity has been defined as “any adverse effect on the chemistry, structure or function of the nervous system, during development or at maturity, induced by chemical or physical influences” (Costa, 1998). An adverse effect is “any treatment related change which interferes with normal function and compromises adaptation to the environment” (ECETOC, 1992). Thus, most morphological changes such as neuronopathy (a loss of neurons), axonopathy (a degeneration of the neuronalaxon), myelinopathy (a loss of the glial cells surrounding the axon), or other gliopathies, would be considered adverse, even if structural and/or functional changes were mild or transitory. In addition, neurochemical changes, also in the absence of structural damage, should also be considered adverse, even if they are transient and reversible, as they bring about dysfunction (Giordano and Costa, 2012). Neurotoxicity can also happen as a result of indirect effects, such as harm to hepatic or cardiovascular structures, or because of interference with the endocrine systems. Some chemicals may have several manners of action and may influence the nervous system both directly and indirectly (Crofton, 2008). Valproic acid (VPA) is a branched chain carboxylic acid (2-propylpentanoic acid or di-n-propylacetic acid), with a chemical structure very resemble to that of short chain fatty acids (Johannessen and Johannessen, 2003). VPA is a drug utilized for treatment of epilepsy, schizoaffective and bipolar disorder. It is also most desirable known as a major antiepileptic drug for generalized and partial seizures in adults and children. Despite its wide spectrum usage, valproate is also well known for its idiopathic deadly side effects such as hepatotoxicity and teratogenicity (Tan et al., 2016), pancreatitis, bone marrow suppression, polycystic ovary syndrome, and VPA-induced hyperammonemic encephalopathy (VHE) (Larsen and Østergaard, 2014) [leading to neurotoxicity and irreversible brain damage (Priester et al., 2009)]. Nigella sativa (NS), usually known as black cumin, belongs to the botanical family of Ranunculaceae which is extensively farmed in the Mediterranean region (Noor et al., 2012). NS has been widely carried out researches for its biological activities and restorative potential and illustrated to have a wide range of activities such as diuretic, antihypertensive, anti-diabetic, anti-cancer, immune-modulatory, antimicrobial, anthelmintic, spasmolytic, bronchodilator, anti-inflammatory, anti- tussive, gastroprotective, hepato-protective, neuroprotective, renal protective and anti-oxidant properties. In traditional medicine, the seeds of NS are generally used as a part of the therapy of various illnesses like obesity, back pain, hypertension and gastrointestinal problems, asthma, cardiac diseases, diarrhea, rheumatoid arthritis and skin disorders (Beheshti et al., 2016). The best part of the corrective properties of this plant is due to the presence of thymoquinone (TQ) which is a major active chemical component of the essential oil (Darakhshan et al., 2015). TQ reported to demonstrate the anticonvulsant activity (Hosseinzadeh et al., 2005) and also show to display neuroprotective effects (El- Dakhakhny et al., 2002). Materials and Methods Preparation of Plant Extract NS seeds were purchased from a local herbalist in Egypt. The seeds were botanically authenticated by