Chronic exposure to MDMA (ecstasy) increases DNA damage in sperm and alters testes histopathology in male rats
ABSTRACT 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is consumed mainly by young population. For this reason, it is especially relevant to take into consideration the effects on the reproductive system. The influence of MDMA on the fertility and reproduction of the male rat was assessed in this study. MDMA was administered subcutaneously at 0 mg/kg (control), 0.5 mg/kg, 5 mg/kg and 10 mg/kg to SD male rats once a day, 3 consecutive days a week during 12 weeks, simulating human weekend associated consumption. Hormonal, haematological, biochemical, histological, genotoxicological and testicular and sperm parameters were evaluated in half of the rats. The remaining animals were mated with untreated sexually receptive females to evaluate the mating and pregnancy rates. A significantly higher incidence of DNA damage in Comet Test in sperm, tubular degeneration and interstitial oedema in testes was found. At all doses tested, sperm motility, morphology, mating and pregnancy rates, and number of implantation sites were not affected. This study fills the existing gap of knowledge about the chronic effects of MDMA in reproductive function using a realistic experimental design. Taking into account the higher sensitivity of human males, some concerns about the effects on the reproductive health still remain.
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ABSTRACT: Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction. We briefly describe a method to systematically identify oxidatively-modified mitochondrial proteins in control and MDMA-exposed rats by using biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins. We also describe various applications and advantages of this Cys-targeted proteomics method and alternative approaches to overcome potential limitations of this method in studying oxidized proteins from MDMA-exposed tissues. Finally we discuss the mechanism of synergistic drug-interaction between MDMA and other abused substances including alcohol (ethanol) as well as application of this redox-based proteomics method in translational studies for developing effective preventive and therapeutic agents against MDMA-induced organ damage.Current pharmaceutical biotechnology 08/2010; 11(5):434-43. DOI:10.2174/138920110791591436 · 2.51 Impact Factor
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ABSTRACT: 3,4-Methylenedioxymethamphetamine, MDMA or "ecstasy" is consumed mainly by young population at childbearing age. Therefore, there may be a risk of exposure of some pregnant women. The effects of the developmental exposure to MDMA on the sexual development and long-term sexual behaviour/fertility were assessed in Sprague-Dawley rats. MDMA was administered subcutaneously at 0 (control), 0.5, 5 and 10 mg/kg to female rats once a day, three consecutive days a week during 10 weeks, including gestation and lactation. The male offspring was evaluated for sexual maturation and mated with untreated sexually receptive females to evaluate the mating and pregnancy rates. Hormonal, haematological, biochemical, histological, genotoxicological and testicular and sperm parameters were also evaluated. A significant higher incidence of DNA damage in sperm and interstitial oedema in testes was found. There was also a significant and dose-related decrease in sperm count and a significant decrease in sperm motility at all doses. A significant delay in preputial separation onset in all treated groups was observed. This study reports by the first time an alteration of spermatogenesis after in utero and lactation MDMA exposure in the rat.Toxicology Letters 08/2010; 197(2):135-42. DOI:10.1016/j.toxlet.2010.05.009 · 3.36 Impact Factor
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ABSTRACT: We have carried out in situ X-ray diffraction experiments on the FeS–H system up to 16.5GPa and 1723K using a Kawai-type multianvil high-pressure apparatus employing synchrotron X-ray radiation. Hydrogen was supplied to FeS from the thermal decomposition of LiAlH4, and FeSHx was formed at high pressures and temperatures. The melting temperature and phase relationships of FeSHx were determined based on in situ powder X-ray diffraction data. The melting temperature of FeSHx was reduced by 150–250K comparing with that of pure FeS. The hydrogen concentration in FeSHx was determined to be x=0.2–0.4 just before melting occurred between 3.0 and 16.5GPa. It is considered that sulfur is the major light element in the core of Ganymede, one of the Galilean satellites of Jupiter. Although the interior of Ganymede is differentiated today, the silicate rock and the iron alloy mixed with H2O, and the iron alloy could react with H2O (as ice or water) or the hydrous silicate before the differentiation occurred in an early period, resulting in a formation of iron hydride. Therefore, Ganymede's core may be composed of an Fe–S–H system. According to our results, hydrogen dissolved in Ganymede's core lowers the melting temperature of the core composition, and so today, the core could have solid FeSHx inner core and liquid FeHx–FeSHx outer core and the present core temperature is considered to be relatively low.Earth and Planetary Science Letters 01/2011; 301(1):153-158. DOI:10.1016/j.epsl.2010.10.033 · 4.72 Impact Factor