Abstract
Induction of hepatic metallothionein (MT) by acetaminophen was characterized in the rat and mouse. Treatment of rats with the hepatotoxin resulted in increase of liver MT in a dose-dependent manner. MT concentration was elevated by 41%, 140% and 260% following acetaminophen injection at doses of 250, 500 and 1000 mg/kg, respectively. The cadmium-binding protein was identified as MT by Sephadex G-75 gel filtration (Ve/Vo = 2.1). In the mouse the hepatotoxin was more potent i.e. maximal effect (increase of 230%) was achieved at the lowest applied dose (250 mg/kg). In both species maximal induction was observed 24 h post exposure and thereafter the hepatic MT content declined, indicating a relatively short half-life of the protein. The elevation of the intracellular concentration of a sulfhydryl-rich protein such as MT may serve as self protecting mechanism of the hepatocyte against highly reactive metabolites of toxic substances.
Original language | English |
---|---|
Pages (from-to) | 323-329 |
Number of pages | 7 |
Journal | Toxicology |
Volume | 53 |
Issue number | 2-3 |
DOIs | |
State | Published - 30 Dec 1988 |
Keywords
- Acetaminophen
- Hepatotoxicity
- Metallothionein