Korean J Physiol Pharmacol.  1998 Apr;2(2):261-269.

Ethanol prevents from acetaminophen inducible hepatic necrosis by inhibiting its metabolic activation in mice

Affiliations
  • 1Department of Pharmacology, College of Pharmacy, Sung Kyun Kwan University, Suwon 440-746, Korea.
  • 2Department of Pharmacology and Toxicology, College of Medicine, Inha University, Inchon 402-751, Korea.

Abstract

Concomitant administration of a single acute dose of ethanol (4 g/kg) protected mice from the hepatocellular injury observed upon administration of a large dose of acetaminophen (400 mg/kg). This was evidenced by the normal histological appearances of liver sections and by the lowered serum aminotransferase activities in mice treated with ethanol and acetaminophen together. In the mice treated with acetaminophen alone, along with the hepatic necrosis, the hepatic microsomal aminopyrine N-demethylase activity was decreased. However, co-administration of ethanol prevented this acetaminophen dependent inhibition on the microsomal mixed function oxidase activity. Pharmacokinetic studies indicated that the concentration of un-metabolized drug in the blood was increased in the ethanol treated mice. Furthermore, upon co-administration of ethanol, although the biliary levels of acetaminophen metabolites (glucuronide, sulfate and cysteine conjugates) were decreased, the level of unmetabolized acetaminophen was increased. Our findings suggest that co-administration of an acute dose of ethanol reduces the degree of hepatocellular necrosis produced by a large dose of acetaminophen and this ethanol dependent protection is, in major part, afforded by suppression of the hepatic microsomal mixed function oxidase activity catalyzing the metabolic activation of acetaminophen.

Keyword

Acetaminophen; Ethanol; Microsomal Mixed Function Oxidase; Conjugation

MeSH Terms

Acetaminophen*
Aminopyrine N-Demethylase
Animals
Biotransformation*
Cysteine
Ethanol*
Liver
Mice*
Necrosis*
Oxidoreductases
Acetaminophen
Aminopyrine N-Demethylase
Cysteine
Ethanol
Oxidoreductases
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