Sayed Masoud Hosseini - Department of Pharmacodynamy and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Elahe Taghiabadi - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Khalil Abnous - Pharmaceutical Research Center, Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Alireza Timcheh Hariri - Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Hamed Pourbakhsh - Food Control Laboratory, Food and Drug Administration, Shiraz University of Medical Sciences, Shiraz, Iran
Hossein Hosseinzadeh - Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): Long term consumption of ethanol may induce damage to many organs. Ethanol induces its noxious effects through reactive oxygen species production, and lipid peroxidation and apoptosis induction in different tissues and cell types. Previous experiments have indicated the antioxidant characteristics of thymoquinone, the active constituent of Nigella sativa fixed oil, against biologically dangerous reactive oxygen species. This experiment was planned to evaluate the protective effect of thymoquinone against subchronic ethanol toxicity in rats. Materials and Methods: Experiments were performed on six groups. Each group consisted of six animals, including control group (saline, gavage), ethanol-receiving group (۳ g/kg/day, gavage), thymoquinone (۲.۵, ۵, ۱۰ mg/Kg/day, intraperitoneally (IP)) plus ethanol and thymoquinone (۱۰ mg/Kg/day, IP) groups. Treatments were carried out in four weeks. Results: Thymoquinone reduced the ethanol-induced increase in the lipid peroxidation and severity of histopathological alteration in liver and kidney tissues. In addition it improved the levels of proinflammatory cytokines in liver tissue. Furthermore, thymoquinone corrected the liver enzymes level including alanine transaminase, aspartate transaminase and alkaline phosphatase in serum and glutathione content in liver and kidney tissues. Other experiments such as Western blot analysis and quantitative real-time RT-PCR revealed that thymoquinone suppressed the expression of Bax/Bcl-۲ ratio (both protein and mRNA level), and caspases activation pursuant to ethanol toxicity. Conclusion: This study indicates that thymoquinone may have preventive effects against ethanol toxicity in the liver and kidney tissue through reduction in lipid peroxidation and inflammation, and also interrupting apoptosis.

Apoptosis, Ethanol toxicity, GSH content, Lipid Peroxidation, Nigella Sativa, Thymoquinone