Alteration in glucose metabolism in the brain associated with tamoxifen treatment: Study in postmenopausal animal model.

Tamoxifen is an effective breast cancer therapy in postmenopausal women. However, it can induce hyperglycemia through different mechanisms, such as the impairment of mitochondrial metabolism. Quercetin, a flavonoid with antioxidant potential, has beneficial effects on tamoxifen-induced adverse effects. Therefore, this study aimed to (1) investigate glucose concentration in blood, cerebrospinal fluid, cerebellum, cortex, and hippocampus of tamoxifen-treated ovariectomized female rats, non-treated and treated with quercetin; and (2) establish the metabolic profile of these regions. For that purpose, ovariectomized female rats were divided into four groups: canola oil 1 mL/kg (CONT); tamoxifen 5 mg/kg (TAM); quercetin 22.5 mg/kg (QUER); and tamoxifen 5 mg/kg + quercetin 22.5 mg/kg (TAM + Q); and were treated for 14 days orally. Subsequently, glucose levels were measured in blood, cerebrospinal fluid, cerebellum, cortex, and hippocampus. Pyruvate and lactate concentrations were analyzed in the three brain regions. Tamoxifen-induced hyperglycemia significantly increased glucose concentrations in the cerebrospinal fluid, cortex, and hippocampus, as well as lactate production in the hippocampus. Quercetin significantly prevented the tamoxifen-induced increase in glucose concentrations in all analyzed samples. Besides, quercetin decreased cortical pyruvate production. The copper content decreased only in the hippocampus of group TAM + Q animals. In addition, it is important to highlight that this study also observed that fourteen days of tamoxifen treatment strongly affects brain glucose metabolism, potentially disrupting normal brain functions. Therefore, this drug might represent a risk factor for postmenopausal women undergoing chemoprevention. Meanwhile, quercetin represents a potential intervention to promote metabolic regulation of glucose in tamoxifen-treated women.

Antihyperglycemic Effect of Quercetin in Ovariectomized Rats Treated with Tamoxifen.

Tamoxifen is effective in breast cancer therapy in postmenopausal women; however, it causes adverse effects that alter the glycolytic pathway and induce hyperglycemia. Quercetin, a flavonoid with antioxidant potential, inhibits butyrylcholinesterase (BuChE), which is positively associated with hyperglycemia. Therefore, this study investigated the effect of quercetin on tamoxifen-induced hyperglycemia, using BuChE activity as a bioindicator in adult ovariectomized Wistar rats. The ovariectomized rats were treated orally for 14 days with different concentrations of quercetin (2.5, 7.5, 22.5, and 67.5 mg.kg-1 b.w.) and tamoxifen (5 mg.kg-1 b.w.). Subsequently, they were euthanized; blood and tissue samples were collected. The following biochemical parameters were analyzed: plasma glucose levels and BuChE activity in the plasma, liver, intestine, and adipose tissue. The most effective dose of quercetin in reducing hyperglycemia was 22.5 mg.kg-1 b.w. (Que/TAM 4.5/1, P < .00000), although the doses of 2.5 (Que/TAM 0.5/1, P < .05) and 7.5 mg.kg-1 b.w. (Que/TAM 1.5/1, P < .05) were also effective. The BuChE activity decreased in the intestine at all tested doses of quercetin coadministered with tamoxifen (P < .01); however, in adipose tissue, there was a biphasic activity with a decrease (P < .05) and increase (P < .05) in activity at doses of 7.5 and 22.5 mg.kg-1 b.w. of quercetin, respectively. However, the correlation between BuChE and glucose levels was not significant (P > .05). In summary, the findings of the present study suggest that quercetin when associated with tamoxifen decreases in plasma glucose levels. Furthermore, in these cases, BuChE should not be used as an indicator of hyperglycemia.

Influence of the Alcohol Present in a Phytotherapic Tincture on Male Rat Lipid Profiles and Renal Function.

This study evaluated the influence of the alcohol present in a formulation of the antiophidic phytotherapic tincture, Específico-Pessôa, on rat blood biochemical and hematological parameters, and on organ histology. Three groups of rats were treated orally for 10, 15, or 30 days; one group received the tincture, the other received alcohol alone, and the third was a control group. The results of this study indicated that cholesterol levels were significantly increased after 10 days in the alcohol and tincture groups, although these decreased after 30 days in the tincture group. Triglyceride levels were significantly reduced after 15 days in the tincture group and after 30 days in the alcohol and tincture groups. A higher creatinine level was observed in the alcohol and tincture groups after 15 and 30 days. The uric acid levels in these groups were reduced at 10 and 30 days, although this metabolite was elevated at 15 days in the alcohol group. Hydropic multifocal degeneration with lymphohistiocytic infiltration and some polymorphonuclear cells was observed in the livers of rats treated with either the tincture or alcohol. These data demonstrate the importance of considering the potential actions of the alcohol present in pharmaceutical formulations.

Influence of tamoxifen on gluconeogenesis and glycolysis in the perfused rat liver.

The actions of tamoxifen, a selective estrogen receptor modulator used in chemotherapy and chemo-prevention of breast cancer, on glycolysis and gluconeogenesis were investigated in the isolated perfused rat liver. Tamoxifen inhibited gluconeogenesis from both lactate and fructose at very low concentrations (e.g., 5µM). The opposite, i.e., stimulation, was found for glycolysis from both endogenous glycogen and fructose. Oxygen uptake was unaffected, inhibited or stimulated, depending on the conditions. Stimulation occurred in both microsomes and mitochondria. Tamoxifen did not affect the most important key-enzymes of gluconeogenesis, namely, phosphoenolpyruvate carboxykinase, pyruvate carboxylase, fructose 1,6-bisphosphatase and glucose 6-phosphatase. Confirming previous observations, however, tamoxifen inhibited very strongly NADH- and succinate-oxidase of freeze-thawing disrupted mitochondria. Tamoxifen promoted the release of both lactate dehydrogenase (mainly cytosolic) and fumarase (mainly mitochondrial) into the perfusate. Tamoxifen (200µM) clearly diminished the ATP content and increased the ADP content of livers in the presence of lactate with a diminution of the ATP/ADP ratio from 1.67 to 0.79. The main causes for gluconeogenesis inhibition are probably: (a) inhibition of energy metabolism; (b) deviation of intermediates (malate and glucose 6-phosphate) for the production of NADPH required in hydroxylation and demethylation reactions; (c) deviation of glucosyl units toward glucuronidation reactions; (d) secondary inhibitory action of nitric oxide, whose production is stimulated by tamoxifen; (e) impairment of the cellular structure, especially the membrane structure. Stimulation of glycolysis is probably a compensatory phenomenon for the diminished mitochondrial ATP production. The multiple actions of tamoxifen at relatively low concentrations can represent a continuous burden to the overall hepatic functions during long treatment periods.

Padronização de spot tests para uso em laboratórios com atendimento em emergências toxicológicas / Using stardardization spot tests in laboratories with toxicological emergencies service

A padronização de métodos simples e confiáveis em laboratórios de análises clínicas que atuam em emergências toxicológicas é importante, visto o alto índice de intoxicações apresetnado nas mais diversas regiões do país. Dentre as intoxicações, as de maior destaque são as medicamentosas. Os medicamentos mais envolvidos são os analgésicos, os benzodiazepínicos e os barbitúricos (fenobarbital). Assim foram padronizados alguns spot tests, segundo Brito Filho, para a pesquisa destes medicamentos em sangue e urina. Os resultados mostraram-se satisfatórios, com valor de sensibilidade de 0,1 e 0,3mg/mL, consistindo em provas simples, rápidas, de baixo-custo e de fácil implantação em laboratórios clínicos.

Intoxicação infantil: experiência de familiares de crianças intoxicadas no município de Maringá (PR) / Family reaction to child poisoning in the municipaly of Maringá - Paraná State

O presente estudo foi realizado com o objetivo de relatar a experiência dos familiares de crianças que se intoxicaram por medicamentos, agrotóxicos de uso doméstico e domissanitários, residentes em Maringá, quanto a identificação do episódio da intoxicação infantil, os cuidados prestados na residência, antes e após a alta dos serviços de saúde e os sentimentos experimentados...

A experiência dos familiares durante a ocorrência da intoxicação infantil no município de Maringá (PR)

Artigo disponibilizado na revista Espaço para a Saúde, versão online. Apresenta estudo realizado com familiares de crianças entre 1 e 6 anos que sofreram intoxicação com medicamentos, agrotóxicos de uso doméstico ou domissanitários, visando contribuir para uma atuação mais efetiva dos profissionais de saúde junto às famílias e a prestação de assistência a partir das perspectivas das pessoas envolvidas.

Analise epidemiologica das tentativas de suicidio atendidas pelo Centro de Controle de Intoxicacoes de Maringa (PR), no periodo de 1991-1994

Foi realizado um estudo exploratorio, abrangendo o periodo de janeiro de 1991 a dezembro de 1994, nos arquivos do Centro de Controle de Intoxicacoes de Maringa: foram levantados 879 casos de tentativas de suicidio, nos quais as variaveis - dados pessoais, substancias utilizadas, associacao com bebidas alcoolicas, incidencia de obitos, necessidade de internamento e o motivo das tentativas de suicidio - foram avaliadas. Foi possivel caracterizar o perfil do potencial paciente suicida atendido em nossa Unidade, como sendo o de um jovem entre 20 e 29 anos, do sexo feminino, residente em zona urbana, que procede ao atentado contra a propria vida devido a conflitos conjugais e familiares, usando medicamentos como agente causal. Os suicidas que obtem exito letal sao do sexo masculino, na proporcao: 12 homens/1 mulher, pertencendo a uma faixa etaria superior a 30 anos (com media das idades de 40,8 anos), utilizando os agrotoxicos como agente causal.

A deplecao do glicogenio hepatico causada pelo paracetamol: estudos in vivo e no figado em perfusao isolada / The depletion of the hepatic glycogen caused by paracetamol: studies in vivo and in the liver in isolate perfusion

Os efeitos do paracetamol sobre varias vias metabolicas foram investigados, em ratos Wistar, nas condicoes in vivo e no figado em perfusao. O paracetamol afetou o metabolismo energetico mitocondrial. A sintese de glicogenio foi inibida pelo paracetamol tanto no figado em perfusao como in vivo. A N-acetilcisteina, que protege os animais contra a deplecao do glicogenio hepatico causada pelo paracetamol, nao afetou a glicolise, a glicogenolise, o consumo de oxigenio e a neoglicogenese. A substancia, no entanto, ativou a sintese de glicogenio tanto na ausencia como tambem na presenca do paracetamol