205 Research Article HEPATO-PROTECTIVE ROLE OF THE AQUEOUS AND N-HEXANE EXTRACTS OF NIGELLA SATIVA LINN. IN EXPERIMENTAL LIVER DAMAGE IN RATS FARIDA YESMIN 1 , ZAIDA RAHMAN 2 , JESMIN FOUZIA DEWAN 3 , ASADUL MAZID HELALI 4 , NOR IZA A RAHMAN 5 , AHMED G. ALATTRAQCHI 6 , AREFUDDIN AHMED 7 , RABEYA YOUSUF 8 , ABDUS SALAM 9 , MAINUL HAQUE 10 1 Assistant Professor, Department of Pharmacology & Therapeutics, Gonoshashthaya Samajvittik Medical College (GSSVMC), Savar, Dhaka, Bangladesh; 2 Associate Professor, Department of Pharmacology & Therapeutics, Enam Medical College & Hospital, Savar, Dhaka, Bangladesh; 3 Professor, Department of Pharmacology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag Dhaka, Bangladesh; 4 Assistant Professor, Department of Pharmacology & Therapeutics, GSSVMC, Dhaka, Bangladesh; 5 Medical Lecturer, Faculty of Medicine and Health Sciences (FPSK), Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia; 6 Medical Lecturer, FPSK, UniSZA, Terengganu, Malaysia; 7 Senior Lecturer, Medical Radiation Programme, School of Health Sciences, Universiti Sains Malaysia, Malaysia; 8 Medical Officer, Blood Bank Unit, Department of Pathology, Universiti Kebangsaan Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia; 9 Associate Professor, Department of Medical Education, UKM Medical Centre, Kuala Lumpur, Malaysia; 10 Professor, FPSK, UniSZA, Terengganu, Malaysia. 10 Email: runurono@gmail.com Received: 13 June 2013, Revised and Accepted: 3 July 2013 ABSTRACT Objective: Liver disease is associated with the formation of oxygen derived free radicals. Reactive oxygen species (ROS) as well as nitrogen species are responsible for nuclear DNA fragmentation and cell death. The active principle of thymoquinone (TQ) of Nigella sativa acts as a scavenger of superoxide anion. The current study was conducted to evaluate the hepatoprotective effect of Nigella sativa on rats. Methods: The study was carried out at prime postgraduate medical University of Bangladesh. Liver damage and oxidative stress were evaluated by measuring serum alanine amino transferase (ALT), hepatic malondialdehyde (MDA) and hepatic Glutathione (GSH) levels. Aqueous extract of Nigella sativa and n-hexane extract of Nigella sativa were administered orally into two groups of rat through intra-gastric tube for 28 days. Both the groups received paracetamol intra-peritoneally on day 28 th and were sacrificed on day 30 th . Subsequently, the following parameters were studied: Serum ALT, hepatic MDA, and hepatic GSH. Results: Hepatic damage was evaluated by significant increases in serum ALT (p<0.001) and hepatic MDA (p<0.001) concentration with depleted hepatic GSH (p<0.001) in paracetamol treated group. Pre-treated with aqueous extract of Nigella sativa significantly reduced serum ALT (p<0.001) and hepatic MDA (p<0.001) levels and also significantly associated with the increase in hepatic GSH (p<0.01). Pretreatment with n-hexane extracts of Nigella sativa decreased serum ALT (p<0.001), hepatic MDA (p<0.001) and increased hepatic GSH (p<0.001). Conclusion: Hepatoprotective properties of Nigella sativa in liver damage of experimental rats by reducing oxidative stress are evident. The protection afforded by the n-hexane extract of Nigella Sativa in pre-treated group has also been validated. Keywords: Hepatoprotective, Liver-damage, Nigella sativa Linn. INTRODUCTION Liver diseases are always dealt very seriously by the graduate physicians due to their potentiality to cause morbidity and mortality. The prevalence rate of liver disease in Bangladesh is the highest in the world [1]. Liver is the main organ involved in the metabolism of biological toxins and medicinal agents [2]. Hence; metabolism is always associated with the disturbance of hepatocyte biochemistry and generation of ROS [3, 4, 5]. ROS are involved in liver damage induced by several conditions such as viral hepatitis [6], alcohol abuse [3], cirrhosis of liver [7], hepatocellular carcinoma [8] and paracetamol-induced liver damage [9]. Paracetamol (acetaminophen) is a safe and effective analgesic and antipyretic drug when used at therapeutic dose [10]. However, an overdose can produce fatal hepatic necrosis in man [11] and other animals [10]. It has been stated that paracetamol overdose is one of the most frequent causes of drug induced liver failure in the United States and in the Great Britain [12]. Previously, researchers studying the toxic mechanism of paracetamol focused on the metabolic activation of the drug by cytochrome P450 enzymes to a reactive metabolite that depleted GSH and covalently bound to protein. Reduced amount of GSH leads covalent binding of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) with cellular protein resulting in hepatic cell death [13, 10]. Current drug for the management of high-dose paracetamol-induced toxicity includes N-acetylcysteine and methionine. They provide protection after paracetamol overdose primarily by replenishment of hepatic GSH stores and direct detoxification of NAPQI. Although these antidotes have been available for more than two decades, they possess certain limitations and hepatic damage and deaths are still frequently seen, largely because of late presentation [14]. Therefore, experiments are being carried out in search of more effective, non-toxic, inexpensive agents. Ample researches have been carried out to obtain appropriate therapy for paracetamol-induced hepatotoxicity as well as different approaches of preventing and treating liver diseases. Antioxidant therapy used in different liver diseases is GSH [13], l-ascorbic acid [15, 16], Andrographis paniculata (kalamegh) [17], Spirulina [18], Cajunus indica (arhar) [19], Phyllanthus niruri (bhuiamla) [20, 21, 22], Silymarin [23], vitamin E [24] and selenium (Se) [25]. The black cumin is an important spice, also known as black seed, fennel flower, nutmeg flower, Roman coriander, or black caraway. N. sativa is a common spice that grows once a year and a member of the Ranunculaceae family [26]. The seeds have traditionally been used in South Asia and Middle Eastern folk medicine as a natural remedy for various diseases as well as spice for over 2000 years. The seeds of N. sativa have been subjected to a range of pharmacological, phytochemical and nutritional investigations. Human studies and laboratory studies on the seeds and oil have been subjected to scientific experiments and have been reported to be effective for immune stimulation and treatment of rheumatism, [27], diabetes [28,29], cancer and inflammatory diseases [30]. The extracts of the black seeds have many therapeutic effects such as antibacterial [31], antifungal [32], anthelmintic [33], analgesic [34], Vol 6, Suppl 3, 2013 ISSN - 0974-2441