Related Experiment Videos
Effect of potassium ethylxanthogenate on the acetaminophen hepatotoxicity in mice
1Institute of Physiology, Bulgarian Academy of Sciences.
Abstract:
The effects of potassium ethylxanthogenate (PEX), acetaminophen (AAP) and their combination on the activity of serum transaminases, liver glutathione level and the activity of some drug metabolizing enzyme systems in male albino mice are studied. PEX (80 mg/kg p. o.), applied one hour before AAP (737.5 mg/kg p. o.) or simultaneously with it, prevents the AAP-induced rise in transaminases. PEX reduces significantly the AAP-induced depletion of the liver glutathione. Eighteen hours after the administration of a hepatotoxic dose of AAP, there is a statistically significant decrease of the activity of aniline hydroxylase, ethylmorphine demethylase, uridine diphosphoglucuronyl transferase, glutathione-S-transferase, NADPH-cytochrome-c-reductase, the P-450 content and a 5-fold increase of TBA-reactive products. PEX, introduced one hour before AAP or simultaneously with it, prevents these changes. The basic mechanism through which PEX reduces the liver toxicity of AAP is assumed to be the decrease in the amount of toxic metabolite formed.
Insights
Potassium ethylxanthogenate (PEX) protects the liver from acetaminophen (AAP) toxicity by preventing harmful metabolic changes. This study shows PEX reduces liver damage markers and preserves enzyme activity when co-administered with AAP.
Area of Science:
- Hepatoprotective agents
- Drug metabolism
- Toxicology
Background:
- Acetaminophen (AAP) overdose is a leading cause of acute liver failure.
- AAP metabolism generates a toxic metabolite responsible for hepatotoxicity.
- Drug-metabolizing enzymes are crucial in xenobiotic detoxification and activation.
Purpose of the Study:
- To investigate the protective effects of potassium ethylxanthogenate (PEX) against AAP-induced liver injury in mice.
- To evaluate the impact of PEX on serum transaminases, liver glutathione levels, and drug-metabolizing enzyme activities following AAP administration.
Main Methods:
- Male albino mice were administered PEX (80 mg/kg) orally before or concurrently with a hepatotoxic dose of AAP (737.5 mg/kg).
- Serum transaminases, liver glutathione levels, and the activity of key drug-metabolizing enzymes (e.g., aniline hydroxylase, ethylmorphine demethylase, CYP450) were measured.
- Levels of TBA-reactive products, an indicator of lipid peroxidation, were assessed.
Main Results:
- PEX administration significantly prevented the AAP-induced elevation of serum transaminases.
- PEX administration attenuated the depletion of liver glutathione caused by AAP.
- PEX treatment preserved the activity of drug-metabolizing enzymes and reduced lipid peroxidation markers (TBA-reactive products) post-AAP exposure.
Conclusions:
- Potassium ethylxanthogenate (PEX) exhibits significant hepatoprotective effects against acetaminophen (AAP)-induced liver toxicity in mice.
- PEX likely mitigates AAP hepatotoxicity by reducing the formation of toxic metabolites.
- These findings suggest PEX as a potential therapeutic agent for acetaminophen poisoning.