Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice.
L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing the beta-oxidation of fatty acid in the mitochondria. It is also a known antioxidant with protective effects against lipid peroxidation. In this study, hepatoprotective effect of L-carnitine was investigated against acetaminophen (AA)-induced liver toxicity where mitochondrial dysfunction and oxidative stress are thought to be involved in AA hepatotoxicity. Sixty-four Balb/C mice were divided into eight groups. Mice were dosed with single-AA injection (500 mg/kg via the intra peritoneal route) with or without L-carnitine (500 mg/kg for 5 days starting 5 days before AA injection via intra peritoneal route) and sampled at 4, 8 and 24 h following AA injection. AA increased serum AST, ALT, total sialic acid (TSA) and MDA as well as tissue TSA and MDA levels significantly with the highest increase observed at 4 h, but there was a decrease in blood and tissue GSH level. Administration of L-carnitine significantly reduced AA-induced elevations in AST, ALT, TSA and MDA concentrations and increased GSH levels at all sampling points. AA also induced necrosis, hyperemia, sinusoidal congestion and hemorrhage with time-dependent increase in severity, but the degree of necrosis and histopathologic alterations were most severe at 24 h following AA administration. However, the degree of pathologic alterations was less severe with simultaneous L-carnitine application. These results suggest that AA results in oxidative damage in the liver with an acute effect. L-carnitine also has a prominent protective effect against AA toxicity and may be of therapeutic value in the treatment of AA-induced hepatotoxicity.
Yapar
Kursad
K
Department of Pharmacology and Toxicology, College of Veterinary Medicine, University of Kafkas, 36040 Kars, Turkey.
Kart
Asim
A
Karapehlivan
Mahmut
M
Atakisi
Onur
O
Tunca
Recai
R
Erginsoy
Serpil
S
Citil
Mehmet
M
D000082:Acetaminophen / Q000633:toxicity*; D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002331:Carnitine / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004336:Drug Antagonism; D005978:Glutathione / Q000097:blood; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid / Q000097:blood; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D014803:Vitamin B Complex / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D014803:Vitamin B Complex; D000082:Acetaminophen; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D019158:N-Acetylneuraminic Acid; D002331:Carnitine