Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver.

This study was undertaken to evaluate the protective effect of thymoquinone (TQ) against acetaminophen-induced hepatotoxicity. Mice were given TQ orally at three different doses (0.5, 1 and 2mg/kg/day) for 5 days before a single hepatotoxic dose of acetaminophen (500 mg/kg i.p.). TQ supplementation dramatically reduced acetaminophen-induced hepatotoxicity, in a dose-dependent manner, as evidenced by decreased serum alanine aminotransferase (ALT) activities. Acetaminophen (500 mg/kg i.p.) resulted in a significant increase in serum ALT and total nitrate/nitrite, hepatic lipid peroxides and a significant decrease in hepatic reduced glutathione (GSH) and ATP in a time-dependent manner. Interestingly, supplementation of TQ (2mg/kg/day) for 5 days before acetaminophen administration resulted in reversal of acetaminophen-induced increase in ALT, total nitrate/nitrite, lipid peroxide and a decrease in GSH and ATP. Moreover, TQ did not affect acetaminophen-induced early decrease in hepatic GSH indicating lack of the effect on the metabolic activation of acetaminophen. In conclusion, TQ is effective in protecting mice against acetaminophen-induced hepatotoxicity possibly via increased resistance to oxidative and nitrosative stress as well as its ability to improve the mitochondrial energy production.

Thymoquinone supplementation induces quinone reductase and glutathione transferase in mice liver: possible role in protection against chemical carcinogenesis and toxicity.

Thymoquinone (TQ), the main constituents of the volatile oil from Nigella sativa seeds is reported to protect laboratory animals against chemical carcinogenesis and toxicity through mechanism(s) that is not fully understood. Among possible mechanism(s), protection could be mediated via induction of detoxifying enzymes, including quinone reductase and glutathione transferase. This study was undertaken to investigate whether oral administration of TQ increases the activities of quinone reductase and glutathione transferase in mice liver. Overdose of TQ, when administered intraperitoneally, caused a marked depletion of hepatic glutathione in both a time- and dose- dependent manner, a characteristic of a group of compounds known as Michael reaction acceptors which are known to act as inducers of enzymes that protect against chemical carcinogenesis and toxicity. TQ was given (1, 2 and 4 mg/kg/day p.o.) for five days to test the chemical inducibility of quinone reductase and glutathione transferase in mice liver. TQ administration produced significant increase in the activities of quinone reductase (147, 196 and 197% of control, respectively) and glutathione transferase (125, 152 and 154% of control, respectively). In conclusion, oral administration of TQ is effective in increasing the activities of quinone reductase and glutathione transferase and makes TQ a promising prophylactic agent against chemical carcinogenesis and toxicity.