Antioxidant and Hepatoprotective Effects of Thymoquinone against Carbon Tetra- Chloride-induced Hepatotoxicity in Isolated Rat Hepatocytes

Herbs are known to play a vital role in the management of various liver diseases. Thymoquinone (TQ) is the bioactive constituent of Nigella sativa seed. The present work was planned to evaluate the potential hepatoprotective effects of TQ against the cytotoxic effects and the oxidative stress induced by carbon tetrachloride (CCl4) in isolated primary rat hepatocytes. Cytotoxicity was determined by assessing cell viability and leakage of cytosolic enzymes, such as lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST). Oxidative stress was assessed by determining reduced glutathione (GSH) level and lipid peroxidation as indicated by thiobarbituric acid reactive substances (TBARS) production. Exposure of isolated rat hepatocytes to CCl4 (5mM) caused cytotoxicity and oxidative injury, manifested by loss of cell viability and significant increase in LDH, ALT and AST leakages. As well as, CCl4 caused progressive depletion of intracellular GSH content and significant enhancement of TBARS accumulation. Preincubation of hepatocytes with either TQ (1mM) or silymarin (5 mM) which is a known hepatoprotective agent, ameliorated the hepatotoxicity and oxidative stress induced by CCl4, as indicated by significant improve in cell viability, significant decrease in LDH, ALT and AST leakages, significant prevent GSH depletion and significant decrease in TBARS formation as compared to CCl4 alone-treated cells. The present results indicate that CCl4 has a potential cytotoxic effect in rat heptocytes; and TQ can afford a significant protection against CCl4 –induced hepatotoxicity.