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.
Nagi
Mahmoud N
MN
Department of Pharmacology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. mnnagi@hotmail.com
Almakki
Hussain A
HA
Sayed-Ahmed
Mohamed M
MM
Al-Bekairi
Abdullah M
AM
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D016227:Benzoquinones; D008054:Lipid Peroxides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D000082:Acetaminophen; D000255:Adenosine Triphosphate; D000410:Alanine Transaminase; D005978:Glutathione; C003466:thymoquinone