Life Science Journal 2014;11(8) http://www.lifesciencesite.com 26 Could Thymoquinone Protect The Liver Against Indomethacin Toxicity? Mohamed Abdelmohsen Abdallah¹* and Mohamed Elsayed Kelany² ¹ Physiology Department, Faculty of Medicine, Menoufeya University, Egypt. ² Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Egypt. * mwmdy@yahoo.com : yasserbast@yahoo.com Abstract: Background: The non-steroidal anti-inflammatory drug indomethacin (IND), utilized in the treatment of inflammatory disorders, has been found to induce liver disorders in both animals and humans. Its administration in a high dose causes hepatic toxicities and results in liver cell deaths by activating multiple stress pathways. Objectives: This study was conducted to investigate the effects of thymoquinone (TQ) on indomethacin-induced hepatotoxicity in rats. Study design: Male adult albino rats were divided into 4 groups: Group I: control non-treated group; the rats were treated orally with normal saline, Group II: TQ-treated (TQ) group; the rats were treated with TQ in the dose of 10 mg/kg/day orally, Group III: single high dose IND- treated (SHDI) group; the rats were treated with IND in the dose of 25 mg/kg once orally at the end of the duration of normal saline treatment, and Group IV: concomitant TQ- and IND- treated (CT/I) group; the rats were treated orally with TQ in the dose of 10 mg/kg/day, and then with IND in the dose of 25 mg/kg once at the end of TQ treatment. The treatment was for 4 weeks for all groups. At the end of the experiment, serum alanine transaminase (ALT), aspartate transaminase (AST), albumin, total antioxidative capacity (TAC) were measured in all rats. Agarose gel electrophoresis for DNA (DNA analysis) for rat’s liver tissue was investigated also after sacrificing the rats. These parameters were expressed as the means of the effects ± SEM. Results: There were significant (P < 0.001) decrease in serum ALT and AST. and significant (P < 0.001) increase in serum TAC and DNA analysis between CT/I group and SHDI group. Albumin was not significantly changed (P > 0.05) between CT/I group and SHDI and control groups. Conclusion: These findings suggested that TQ is strong protective agent against IND-induced hepatotoxicity in rats. The collective data demonstrated that TQ has the potential to scavenge oxidants and decrease apoptotic changes and revealed a possible protective target mechanism for the damaging effects of IND on liver in rats. [Mohamed Abdelmohsen Abdallah and Mohamed Elsayed Kelany. Could Thymoquinone Protect The Liver Against Indomethacin Toxicity? Life Sci J 2014;11(8):26-33]. (ISSN:1097-8135). http://www.lifesciencesite.com . 4 Keywords: Thymoquinone, Indomethacin, apoptosis, oxidation. 1. Introduction Drug-induced liver injury is the leading cause of acute liver failure and transplantation in western countries. The frequent involvement of the liver in drug-induced toxicity depends on its anatomical location (as it is the primary port of entry for ingested drugs) and its physiological and biochemical functions because of the abundance of metabolizing enzymes. The detection of new drugs that have protective effects against drug-induced hepatotoxicity is a major challenge in clinical practice (Grattagliano et al., 2009). The adverse effects of the non-steroidal anti- inflammatory drug indomethacin (IND) involve the gastrointestinal tract, liver and CNS in both animals and humans. IND causes a decrease of hepatic microsomal cytochrome P-450 dependent monooxygenase system and prostaglandin depletion (Falzon et al., 1985, Whiting et al., 1987 & Nancy Perron et al., 2013). Grattagliano et al. (2005) stated that, hepatic clearance of drugs depends on the activity of transport proteins that are located on the hepatocyte canalicular membrane. Alterations of these transporters by drugs or genetic polymorphisms increase the susceptibility to cholestasis injury which is one of the most important features of drug-induced hepatotoxicity. Substrates for hepatic transport proteins include IND, statins, and other drugs (Grattagliano et al., 2009). Although the underlying molecular mechanisms of IND-induced hepatotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in producing this hepatotoxicity (Rudnick et al., 2006). IND overdose potentially damages the liver by activating multiple stress pathways and causes hepatic disorders (Rudnick et al., 2006, Maity et al., 2009). In the late era, the use of herbal therapies for the prevention and treatment of certain diseases is increased. Nigella sativa (N. sativa) is used as a food condiment in the Middle East, and its seeds/oil possesses anti-inflammatory, antiviral and antineoplastic activities in various in vitro and in vivo studies (Zaher et al., 2008). Gali-Muhtasib et al. (2004) declared that, The black seed herb grows in