O femproporex é o segundo anorexígeno à base de anfetamina mais consumido no mundo; esse fármaco é rapidamente convertido in vivo em anfetamina e atua através do aumento dos níveis de dopamina na fenda sináptica. Considerando que os efeitos do femproporex sobre o Sistema Nervoso Central são ainda pouco conhecidos e que a acetilcolinesterase é uma enzima reguladora envolvida na transmissão colinérgica e que indiretamente pode modular a liberação de dopamina, o presente estudo investigou os efeitos da administração aguda de femproporex sobre a atividade da enzima acetilcolinesterase em cérebro de ratos jovens. Ratos Wistar machos jovens receberam uma única injeção de femproporex (6,25, 12,5 ou 25 mg/kg i.p.) ou veículo (Tween 80 2%). Duas horas após a injeção, os ratos foram mortos por decapitação e o cérebro foi removido para avaliação da atividade da acetilcolinesterase. Os resultados mostraram que a administração de femproporex aumentou a atividade da acetilcolinesterase no hipocampo e córtex posterior, enquanto que no córtex pré-frontal, estriado e cerebelo a atividade da enzima não foi alterada. Em conclusão, o presente estudo demonstrou que a administração aguda de femproporex exerce um efeito no sistema colinérgico causando um aumento na atividade da acetilcolinesterase, de um modo dose dependente, no hipocampo e córtex posterior. Assim, sugere-se que o desequilíbrio na homeostase colinérgica pode ser considerado um importante mecanismo fisiopatológico subjacente ao dano cerebral observado em pacientes que utilizam anfetaminas, como o femproporex.

Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

A primaquina e cloroquina são utilizadas para o tratamento da malária; evidências da literatura sugerem que estes fármacos podem induzir o estresse oxidativo. Neste estudo investigou-se os efeitos da primaquina e cloroquina sobre danos oxidativo e ao DNA no cérebro, fígado e rim de ratos após 7, 14 e 21 dias de administração. Nossos resultados demonstraram que a primaquina causou dano ao DNA no cérebro após 7, 14 e 21 dias, e no fígado após 7 e 14 dias. Além disso, a primaquina aumentou os níveis de TBARS no rim e a carbonilação de proteínas no cérebro após 14 dias, e diminuiu a carbonilação de proteínas no fígado após 7 dias. Enquanto que a cloroquina causou dano ao DNA no rim após 7 e 14 dias, e no fígado e cérebro após 14 e 21 dias, aumentou os níveis de TBARS após 7 dias no rim, e reduziu os níveis de TBARS no cérebro após 21 dias. Além disso, diminuiu a carbonilação de proteínas no fígado após 7 e 14 dias, e no cérebro após 7 e 21 dias. Entretanto, o tratamento com cloroquina durante 14 dias aumentou a carbonilação de proteínas no cérebro e rim. Em conclusão, estes resultados mostraram que o tratamento prolongado com antimaláricos pode afetar adversamente o DNA.

Primaquine and chloroquine are used for the treatment of malaria; evidence from the literature suggests that these drugs may induce oxidative stress. In this study we investigated the effects of primaquine and chloroquine on oxidative damage and DNA damage in brain, liver and kidney of rats after 7, 14 and 21 days of administration. Our results demonstrated that primaquine causes DNA damage in brain after 7, 14 and 21 days, and in liver after 7 and 14 days. Moreover, primaquine increases TBARS levels in the kidney and protein carbonyls in the brain after 14 days, and decreases protein carbonyls in the liver after 7 days. Whereas chloroquine causes DNA damage in the kidney after 7 and 14 days, and in the liver after 14 and 21 days, increases TBARS levels in the kidney after 7 days, and decreases TBARS levels in the brain after 21 days. Moreover, decreases protein carbonyls in the liver after 7 and 14 days, and in the brain after 7 and 21 days. However, chloroquine treatment for 14 days increases protein carbonyls in the brain and kidney. In conclusion, these results showed that prolonged treatment with antimalarial may adversely affect the DNA.

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Methods: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Results: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Conclusion: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability.

OBJECTIVE: Oxidative stress plays an important role in skeletal muscle damage in sepsis. Aerobic exercise can decrease oxidative stress and enhance antioxidant defenses. Therefore, it was hypothesized that aerobic exercise training before a sepsis stimulus could attenuate skeletal muscle damage by modulating oxidative stress. Thus, the aim of this study was to evaluate the effects of aerobic physical preconditioning on the different mechanisms that are involved in sepsis-induced myopathy. METHODS: Male Wistar rats were randomly assigned to either the untrained or trained group. The exercise training protocol consisted of an eight-week treadmill program. After the training protocol, the animals from both groups were randomly assigned to either a sham group or a cecal ligation and perforation surgery group. Thus, the groups were as follows: sham, cecal ligation and perforation, sham trained, and cecal ligation and perforation trained. Five days after surgery, the animals were euthanized and their soleus and plantaris muscles were harvested. Fiber cross-sectional area, creatine kinase, thiobarbituric acid reactive species, carbonyl, catalase and superoxide dismutase activities were measured. RESULTS: The fiber cross-sectional area was smaller, and the creatine kinase, thiobarbituric acid reactive species and carbonyl levels were higher in both muscles in the cecal ligation and perforation group than in the sham and cecal ligation and perforation trained groups. The muscle superoxide dismutase activity was higher in the cecal ligation and perforation trained group than in the sham and cecal ligation and perforation groups. The muscle catalase activity was lower in the cecal ligation and perforation group than in the sham group. CONCLUSION: In summary, aerobic physical preconditioning prevents atrophy, lipid peroxidation and protein oxidation and improves superoxide dismutase activity in the skeletal muscles of septic rats.