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Changes in the hepatic copper conent after treatment with foreign compounds
Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
|January 1, 1978
Summary
Certain compounds affect liver copper levels. Disulfiram and pyrazole significantly increase hepatic copper, potentially due to cholestatic effects, while chelators have minimal impact.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Hepatic copper accumulation is implicated in various liver diseases.
- Understanding the influence of xenobiotics on copper metabolism is crucial for therapeutic and toxicological assessments.
Purpose of the Study:
- To investigate the effects of specific compounds, including chelators and other agents, on hepatic copper content in rats.
- To elucidate the mechanisms underlying changes in liver copper levels induced by these substances.
Main Methods:
- Adult male albino rats were administered dimercaprol, CaNa2EDTA, D-penicillamine, diethyldithiocarbamate, disulfiram, pyrazole, and phenobarbital via subcutaneous or intragastric routes.
- Treatments were administered for 4 or 7 days.
- Hepatic copper content was quantified using atomic absorption spectrophotometry on crude homogenates.
Main Results:
- Metal chelating agents (dimercaprol, D-penicillamine, diethyldithiocarbamate) showed only minor reductions in liver copper.
- CaNa2EDTA had no significant effect on hepatic copper levels.
- Phenobarbital treatment resulted in a slight decrease in copper.
- Disulfiram and pyrazole markedly increased hepatic copper content by 3-fold and 2-fold, respectively.
Conclusions:
- Disulfiram and pyrazole induce significant hepatic copper accumulation in rats.
- The observed increase in liver copper by disulfiram and pyrazole is suggested to be a consequence of their cholestatic actions.
- The efficacy of tested chelating agents in reducing hepatic copper was limited under the study conditions.