RESUMO
The study of polyphenols' effects on health has been gaining attention lately. In addition to reacting with important enzymes, altering the cell metabolism, these substances can present either positive or negative metabolic alterations depending on their consumption levels. Naringenin, a citrus flavonoid, already presents diverse metabolic effects. The objective of this work was to evaluate the effect of maternal naringenin supplementation during pregnancy on the tricarboxylic acid cycle activity in offspring's cerebellum. Adult female Wistar rats were divided into two groups: (1) vehicle (1 ml/kg by oral administration (p.o.)) or (2) naringenin (50 mg/kg p.o.). The offspring were euthanised at 7th day of life, and the cerebellum was dissected to analyse citrate synthase, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH) and malate dehydrogenase (MDH) activities. Molecular docking used SwissDock web server and FORECASTER Suite, and the proposed binding pose image was created on UCSF Chimera. Data were analysed by Student's t test. Naringenin supplementation during pregnancy significantly inhibited IDH, α-KGDH and MDH activities in offspring's cerebellum. A similar reduction was observed in vitro, using purified α-KGDH and MDH, subjected to pre-incubation with naringenin. Docking simulations demonstrated that naringenin possibly interacts with dehydrogenases in the substrate and cofactor binding sites, inhibiting their function. Naringenin administration during pregnancy may affect cerebellar development and must be evaluated with caution by pregnant women and their physicians.
Assuntos
Cerebelo/enzimologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Suplementos Nutricionais , Flavanonas/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Animais , Citrato (si)-Sintase/efeitos dos fármacos , Feminino , Isocitrato Desidrogenase/efeitos dos fármacos , Complexo Cetoglutarato Desidrogenase/efeitos dos fármacos , Malato Desidrogenase/efeitos dos fármacos , Simulação de Acoplamento Molecular , Gravidez , Ratos , Ratos WistarRESUMO
Elicitors are compounds or factors capable of triggering a defense response in plants. This kind of response involves signal transduction pathways, second messengers and events such as Reactive Oxygen Species (ROS) generation, proline accumulation and secondary metabolite production. Anthraquinone (AQs) biosynthesis in Rubia tinctorum L. involves different metabolic routes, including shikimate and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways. It has been proposed that the proline cycle could be coupled with the pentose phosphate pathway (PPP), since the NADP+ generated by this cycle could act as a cofactor of the first enzymes of the PPP. The end-product of this pathway is erithrose-4-phosphate, which becomes the substrate of the shikimate pathway. The aim of this work was to study the effect of methyl jasmonate (MeJ), a well-known endogenous elicitor, on the PPP, the proline cycle and AQs production in R. tinctorum cell suspension cultures, and to elucidate the role of ROS in MeJ elicitation. Treatment with MeJ resulted in AQs as well as proline accumulation, which was mimicked by the treatment with a H2O2-generating system. Both MeJ-induced effects were abolished in the presence of diphenyliodonium (DPI), a NADPH oxidase inhibitor (main source of ROS). Treatment with the elicitor failed to induce PPP; therefore, this route did not turn out to be limiting the carbon flux to the shikimate pathway.
Assuntos
Acetatos/farmacologia , Antraquinonas/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Prolina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rubia/metabolismo , Antraquinonas/análise , Compostos de Bifenilo/farmacologia , Ciclo do Carbono , Sobrevivência Celular , Células Cultivadas , Eritritol/análogos & derivados , Eritritol/metabolismo , Glutamato Desidrogenase/efeitos dos fármacos , Glutamato Desidrogenase/metabolismo , Peróxido de Hidrogênio/metabolismo , Isocitrato Desidrogenase/efeitos dos fármacos , Isocitrato Desidrogenase/metabolismo , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , Via de Pentose Fosfato/efeitos dos fármacos , Imunidade Vegetal , Prolina/análise , Prolina/efeitos dos fármacos , Rubia/citologia , Rubia/enzimologia , Rubia/crescimento & desenvolvimento , Transdução de Sinais , Fosfatos Açúcares/metabolismo , Fatores de TempoRESUMO
The activity of cytosolic NADP-linked isocitrate dehydrogenase (ICDH) in rat liver was determined. The administration of 2-bromo-alpha-ergocryptine (CB-154) to male rats produced a significant increase of the enzyme activity and a decrease of serum prolactin (PRL) levels in relation to control animals. Male rats 21 days after castration had lower levels of serum prolactin and higher activity of the enzyme than controls. Injection of PRL to castrated male rats lowered the enzymatic activity to control values. In intact rats injected with prolactin, the activity of the enzyme also decreased. Female rats were separated into the following groups: (a) virgins; (b) rats on day 15 of lactation; (c) ovariectomized rats. The enzymatic activity was similar in the different groups, but significantly higher than in male rats. However, serum PRL was significantly increased in 15 days lactating rats and decreased in ovariectomized ones in relation to virgins. We conclude that PRL regulates hepatic ICDH activity in male, but not in female rats. Incubation of isolated hepatocytes from intact or castrated male rats maintained the difference in ICDH activity observed in vivo, while there were no differences in ICDH activity in non-parenchymal cells. Addition of PRL, CB-154, androgens or antiandrogens to isolated hepatocytes from intact and castrated rat, had no effect on the ICDH activity, suggesting that the effect of PRL is exerted at the transcriptional level.