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Published on: June 17, 2016
N-methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: oxidative stress after acute and chronic
Background:
The underlying mechanisms of N-methyl-3,4-methylenedioxyamphetamine--MDMA--induced hepatotoxicity are still unknown. The aim of this study was to evaluate hepatic oxido-reductive status in the rats liver after the single and repeated administration of MDMA.
Methods:
MDMA was dissolved in distilled water and administered in the doses of 5 mg, 10 mg, 20 mg, and 40 mg/kg. The animals from the acute experiment were treated per os with the single dose of the appropriate solution, through the orogastric tube. The animals from the chronic experiment were treated per os, with the doses of 5, 10, or 20 mg/kg of MDMA every day during 14 days. The control groups were treated with water only. Eight hours after the last dose, the animals were sacrificed, dissected, their livers were rapidly removed, frozen and stored at -70 degrees C until the moment of analysis. The parameters of oxidative stress in the crude mitochondrial fractions of the livers were analyzed.
Results:
Superoxide dismutase (SOD) activity increased in the livers of the animals that were treated with single doses of MDMA. Chronically treated animals showed the increased SOD activity only after the highest dose (20 mg/kg). The content of reduced glutathione decreased in both groups, but the depletion was much more expressed after the single administration. Lipid peroxidation index increased in dose-dependent manner in both groups, being much higher after the single administration.
Conclusion:
The increased index of lipid peroxidation and the decreased reduced glutathione levels suggested that MDMA application induced the state of oxidative stress in the liver. These changes were much more expressed after the single administration of MDMA.
Insights
MDMA administration causes oxidative stress in rat livers, indicated by increased lipid peroxidation and decreased glutathione. These effects are more pronounced after a single dose, suggesting acute MDMA exposure is more damaging.
Area of Science:
- Toxicology
- Hepatology
- Biochemistry
Background:
- The mechanisms of MDMA-induced liver damage remain unclear.
- This study investigates the impact of MDMA on the liver's oxidative balance.
Purpose of the Study:
- To evaluate the hepatic oxido-reductive status following single and repeated MDMA administration in rats.
Main Methods:
- Rats received single or daily oral doses of MDMA (5-40 mg/kg) for 14 days.
- Liver mitochondrial fractions were analyzed for oxidative stress markers.
- Parameters included superoxide dismutase activity, reduced glutathione, and lipid peroxidation.
Main Results:
- Single MDMA doses increased superoxide dismutase activity and lipid peroxidation, while decreasing glutathione.
- Chronic MDMA administration elevated superoxide dismutase only at the highest dose, with significant glutathione depletion and lipid peroxidation.
- Oxidative stress markers were more pronounced after single MDMA administration.
Conclusions:
- MDMA induces oxidative stress in the liver, evidenced by increased lipid peroxidation and reduced glutathione.
- Acute MDMA exposure leads to more severe oxidative stress compared to chronic exposure.
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