N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration
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 d...
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Military Health Department, Ministry of Defance, Serbia
2004-01-01
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doaj-597734ba1367408bbbe9879479bf6f842020-11-24T23:18:38ZengMilitary Health Department, Ministry of Defance, SerbiaVojnosanitetski Pregled0042-84502004-01-0161212513110.2298/VSP0402125NN-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administrationNinković MilicaMaličević ŽivoradSelaković Vesna M.Simić IvanVasiljević Ivana D.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°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.http://www.doiserbia.nb.rs/img/doi/0042-8450/2004/0042-84500402125N.pdfN-Methyl-34-methylenedioxyamphetaminedrug toxicityliveroxidative stresslipid peroxidationglutathione |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ninković Milica Maličević Živorad Selaković Vesna M. Simić Ivan Vasiljević Ivana D. |
spellingShingle |
Ninković Milica Maličević Živorad Selaković Vesna M. Simić Ivan Vasiljević Ivana D. N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration Vojnosanitetski Pregled N-Methyl-3 4-methylenedioxyamphetamine drug toxicity liver oxidative stress lipid peroxidation glutathione |
author_facet |
Ninković Milica Maličević Živorad Selaković Vesna M. Simić Ivan Vasiljević Ivana D. |
author_sort |
Ninković Milica |
title |
N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration |
title_short |
N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration |
title_full |
N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration |
title_fullStr |
N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration |
title_full_unstemmed |
N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration |
title_sort |
n-methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: oxidative stress after acute and chronic administration |
publisher |
Military Health Department, Ministry of Defance, Serbia |
series |
Vojnosanitetski Pregled |
issn |
0042-8450 |
publishDate |
2004-01-01 |
description |
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°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. |
topic |
N-Methyl-3 4-methylenedioxyamphetamine drug toxicity liver oxidative stress lipid peroxidation glutathione |
url |
http://www.doiserbia.nb.rs/img/doi/0042-8450/2004/0042-84500402125N.pdf |
work_keys_str_mv |
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