Effects of 3-methylcholanthrene or diethyl maleate on the hepatotoxicity of acetaminophen.
This report presents a set of investigations on the hepatotoxic action of acetaminophen (AA). Male mice of Balb C strain were given [3H]acetaminophen in doses of 100, 300 and 600 mg kg-1 with or without pretreatment with 3-methylcholanthrene (3MCh) or diethyl maleate (DEM). The results of this study show that AA administered in moderate doses brings about necrotic changes due to adduct formation with macromolecules. Adduct formation was inversely correlated with the level of glutathione. Both modifiers enhanced hepatic necrosis and lethality. Diethyl maleate exerted these effects without enhancing covalent binding to macromolecules, while 3MCh increased both adduct formation and lipid peroxidation.
Szymańska
J A
JA
Department of Toxicological Chemistry, Medical Academy, Lódź, Poland.
Swietlicka
E A
EA
Piotrowski
J K
JK
Skrzypińska-Gawrysiak
M
M
Sporny
S
S
D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008298:Maleates / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C
D008298:Maleates; D000082:Acetaminophen; D008315:Malondialdehyde; D008748:Methylcholanthrene; D000410:Alanine Transaminase; C014476:diethyl maleate; D005978:Glutathione