Browsing by Author "Pereira, Maria de Lourdes"
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- Effect of 3,4-methylenedioxymethamphetamine ("ecstasy") on body temperature and liver antioxidant status in mice: influence of ambient temperaturePublication . Carvalho, Márcia; Carvalho, Félix; Remião, Fernando; Pereira, Maria de Lourdes; Pires-das-Neves, Ricardo; Bastos, Maria de LourdesThe consumption of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is known to cause severe hyperthermia and liver damage in humans. The thermogenic response induced by MDMA is complex and partially determined by the prevailing ambient temperature (AT). This is of extreme importance since ecstasy is often consumed at "rave" parties, where dancing takes place in a warm environment, which may exacerbate the effect of MDMA on thermoregulation. In view of the fact that hyperthermia is a well-known pro-oxidant aggressive condition, its potential role in ecstasy-induced hepatocellular toxicity should be further studied. Thus, the present study was performed in order to evaluate the influence of AT on the effects of single administration of MDMA on body temperature and liver toxicity in Charles River mice. Animals were given an acute intraperitoneal dose of MDMA (5, 10 or 20 mg/kg) and placed in AT of 20+/-2 degrees C or 30+/-2 degrees C for 24 h. Body temperature was measured during the study using implanted transponders and a temperature probe reading device. Plasma and liver samples were used for biochemical analysis. Liver sections were also taken for histological examination. The parameters evaluated were (1) plasma levels of transaminases and alkaline phosphatase, (2) hepatic glutathione (GSH), (3) hepatic lipid peroxidation, (4) activity of hepatic antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, glutathione- S-transferase, copper/zinc superoxide dismutase and manganese superoxide dismutase), and (5) liver histology. The hyperthermic response elicited by MDMA was clearly dose-related and potentiated by high AT. Administration of MDMA produced some evidence of oxidative stress, expressed as GSH depletion at both ATs studied, as well as by lipid peroxidation and decreased catalase activity at high AT. High AT, by itself, decreased glutathione peroxidase activity. Histological examination of the liver revealed abnormalities of a dose- and AT-dependent nature. These changes included vacuolation of the hepatocytes, presence of blood clots and loss of typical hepatic cord organisation. The results obtained in the present study suggest that oxidative stress plays a part in the first stage of MDMA-induced liver damage and that liver antioxidant status is aggravated by increased AT. Thus, these findings are in accordance with the hypothesis that high AT may potentiate ecstasy-induced hepatotoxicity by increasing body hyperthermia.
- Protective activity of hesperidin and lipoic acid against sodium arsenite acute toxicity in micePublication . Pires das Neves, Ricardo; Carvalho, Félix; Carvalho, Márcia; Fernandes, Eduarda; Soares, Elisa; Bastos, Maria de Lourdes; Pereira, Maria de LourdesThe objective of the present work was to evaluate the toxic effects of sodium arsenite, As(III), in mice and the protective effect of 2 antioxidants, hesperidin and lipoic acid, against the observed As(III)-induced toxicity. In each study, mice were assigned to 1 of 4 groups: control, antioxidant, antioxidant + arsenite, and arsenite. Animals were first injected with the vehicle or 25 mg antioxidant/kg BW. After 30 minutes they received an injection of 10 mg arsenite/kg BW or 0.9% NaCl. Two hours after the first injection, the liver, kidney, and testis were collected for histological evaluation. Liver samples were also taken for quantification of arsenic. In mice exposed only to As(III), various histopathological effects were observed in the liver, kidneys, and testes. In mice pretreated with either hesperidin or lipoic acid, a reduction of histopathologic effects on the liver and kidneys was observed. No protective effects were observed in the testes for either of the 2 studied antioxidants. In conclusion, hesperidin and lipoic acid provided protective effects against As(III)-induced acute toxicity in the liver and kidneys of mice. These compounds may potentially play an important role in the protection of populations chronically exposed to arsenic.
- Repeated administration of d-amphetamine results in a time-dependent and dose-independent sustained increase in urinary excretion of p-hydroxyamphetamine in micePublication . Carvalho, Félix; Soares, Maria Elisa; Fernandes, Eduarda; Remião, Fernando; Carvalho, Márcia; Duarte, José Alberto; Pires-das-Neves, Ricardo; Pereira, Maria de Lourdes; Bastos, Maria de LourdesThe biotransformation of d-amphetamine into p-hydroxyamphetamine (HA) by cytochrome P450 occurs in several species besides humans. The extent of HA excretion varies among species and the oxidative pathway involved in this biotransformation is reported to be implicated in the toxic effects of d-amphetamine. The aim of this study was to evaluate the influence of dose and repeated administration of d-amphetamine on the urinary excretion of d-amphetamine and HA in mice. Charles River Caesarian Derived (CD)-1 mice, kept in metabolic cages, were treated with d-amphetamine (5, 10 and 20 mg/kg, i.p., daily, for 14 days). Urine was collected at 24 hr intervals and analyzed by HPLC for the quantification of d-amphetamine and HA. Urinary excretion of d-amphetamine increased in a dose dependent manner, the urinary levels being fairly constant after the 4th day. On the other hand the urinary excretion of HA increased during the whole time of d-amphetamine dosing and was not dose dependent. Cortical tubule degeneration was observed for the two higher doses, which may explain the HA excretion pattern, although inhibition of cytochrome P450 (CYP) after high d-amphetamine dosing may also be involved.