Upregulation of Chemoprotective Enzymes and Glutathione by Nigella sativa (Black Seed) and Thymoquinone in CCl4-Intoxicated Rats

To examine the hepatoprotective activities of Nigella sativa (Ns) and thymoquinone (TQ) against carbon tetrachloride (CCl4)induced hepatotoxicity, the effects of water extract of Ns seeds (50 mg/kg) or TQ (5 mg/kg in corn oil) by gavage for 5 days on detoxifying enzymes and glutathione were compared in healthy and CCl4-challenged (1 mL/kg in corn oil, intraperitoneally [ip], a single dose) rats. Both Ns and TQ countered the elevations in serum alanine aminotransferase activity, oxidized glutathione level, and stress ratio caused by CCl4. Both Ns and TQ ameliorated the reductions in the activities and messenger RNA (mRNA) levels of glutathione S-transferase, NAD(P)H-quinone oxidoreductase, and microsomal epoxide hydrolase, as well as the reductions in reduced glutathione and cysteine levels produced by CCl4. In many instances, Ns was much superior to TQ in providing protection against the damaging effects caused by CCl4. This protection could be attributed to the induction of chemoprotective enzymes probably through increasing transcription.