Attenuation of acetaminophen hepatitis by prostaglandin E2. A histopathological study.
Acute acetaminophen hepatitis was produced in three groups of five rats given 1600 mg/kg by gavage. The protective effect of 16,16-dimethyl prostaglandin E2, 200 micrograms/kg administered subcutaneously 30 min later, was compared to the protective effect of N-acetylcysteine 1 g/kg similarly administered. All animals were killed at 24 hr, and liver tissues were compared histologically to the damage found in acetaminophen-treated controls and untreated anatomic controls. Serum transaminase values at 24 hr exceeded 1000 units in the acetaminophen control group, averaged 658 units in the acetylcysteine treated group, and were near normal (75 units) in the prostaglandin treated group (P < 0.02). Liver samples (1 cm3) were removed terminally at 24 hr. Liver damage was assessed without reference to precedent history. Histopathologically, damage was most severe in the acetaminophen control group, mainly in pericentral lobular zones. The prostaglandin-treated group showed considerably less damage, which was confined to the hepatic vein area. The acetylcysteine-treated group showed an intermediate degree of damage. We conclude that dmPGE2, given 30 min after ingestion of acetaminophen was found to be more effective in limiting liver damage than NAC in this rat model.
Monto
G L
GL
Academic Department of Medicine, Royal Free Hospital School of Medicine, University of London, UK.
Scheuer
P J
PJ
Hansing
R L
RL
Burroughs
A K
AK
D015064:16,16-Dimethylprostaglandin E2 / Q000627:therapeutic use*; D000082:Acetaminophen / Q000633:toxicity*; D000111:Acetylcysteine / Q000627:therapeutic use; D000208:Acute Disease; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000082:Acetaminophen; D015064:16,16-Dimethylprostaglandin E2; D000111:Acetylcysteine