Prophylactic and Therapeutic Potential of Acetyl-L-carnitine against Acetaminophen-Induced Hepatotoxicity in Mice.
Prophylactic and therapeutic effects of acetylcarnitine against acetaminophen-induced hepatotoxicity were studied in mice. To evaluate the prophylactic effects of acetylcarnitine, mice were supplemented with acetylcarnitine (2 mmol/kg/day per oral (p.o.) for 5 days) before a single dose of acetaminophen (350 mg/kg intraperitoneal (i.p.)). Animals were sacrificed 6 h after acetaminophen injection. Acetaminophen significantly increased the markers of liver injury, hepatic reactive oxygen species, and nitrate/nitrite, and decreased hepatic glutathione (GSH) and the antioxidant enzymes. Acetylcarnitine supplementation resulted in reversal of all biochemical parameters toward the control values. To explore the therapeutic effects of acetylcarnitine, mice were given a single dose of acetylcarnitine (0.5, 1, and 2 mmol/kg p.o.) 1.5 h after acetaminophen. Animals were sacrificed 6 h after acetaminophen. Acetylcarnitine administration resulted in partial reversal of liver injury only at 2 mmol/kg p.o. At equimolar doses, N-acetylcystiene was superior as therapeutic agent to acetylcarnitine. However, acetylcarnitine potentiated the effect of N-acetylcystiene in the treatment of acetaminophen toxicity.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia. mnnagi@hotmail.com.
Salman A
SA
Alotaibi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Abdulrazaq
A
Alanazi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Saleh A
SA
Bakheet
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Naif O
NO
Alharbi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
Mahmoud N
MN
Nagi
D000082:Acetaminophen / Q000633:toxicity*; D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology
D000975:Antioxidants; D020011:Protective Agents; D000082:Acetaminophen; D000108:Acetylcarnitine
Acetaminophen; Acetyl-l-carnitine; Antioxidant enzymes; Glutathione; Hepatotoxicity; Nitric oxide; Reactive oxygen species