RESUMO
Central administration of valine has been shown to cause hyperphagia in fish. Although mechanistic target of rapamycin (mTOR) is involved in this response, the contributions to feed intake of central and peripheral metabolite changes due to excess valine are unknown. Here, we investigated whether intracerebroventricular injection of valine modulates central and peripheral metabolite profiles and may provide insights into feeding response in fish. Juvenile rainbow trout (Oncorhynchus mykiss) were administered an intracerebroventricular injection of valine (10 µg·µL-1 at 1 µL·100·g-1 body wt), and the metabolite profile in plasma, hypothalamus, and rest of the brain (composing of telencephalon, optic tectum, cerebellum, and medulla oblongata) was carried out by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. Valine administration led to a spatially distinct metabolite profile at 1 h postinjection in the brain: enrichment of amino acid metabolism and energy production pathways in the rest of the brain but not in hypothalamus. This suggests a role for extrahypothalamic input in the regulation of feed intake. Also, there was enrichment of several amino acids, including tyrosine, proline, valine, phenylalanine, and methionine, in plasma in response to valine. Changes in liver transcript abundance and protein expression reflect an increased metabolic capacity, including energy production from glucose and fatty acids, and a lower protein kinase B (Akt) phosphorylation in the valine group. Altogether, valine intracerebroventricular administration affects central and peripheral metabolism in rainbow trout, and we propose a role for the altered metabolite profile in modulating the feeding response to this branched-chain amino acid.NEW & NOTEWORTHY Valine causes hyperphagia in fish when it is centrally administered; however, the exact mechanisms are far from clear. We tested how intracerebroventricular injection of valine in rainbow trout affected the brain and plasma metabolome. The metabolite changes in response to valine were more evident in the rest of the brain compared with the hypothalamus. Furthermore, we demonstrated for the first time that central valine administration affects peripheral metabolism in rainbow trout.
Assuntos
Hipotálamo , Oncorhynchus mykiss , Valina , Animais , Oncorhynchus mykiss/metabolismo , Oncorhynchus mykiss/sangue , Valina/farmacologia , Valina/administração & dosagem , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Metabolômica , Injeções Intraventriculares , Metabolismo Energético/efeitos dos fármacosRESUMO
BACKGROUND: Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties. OBJECTIVES: The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C. METHODS: The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis. RESULTS: The elimination half-life (t1/2Êz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent. CONCLUSIONS: While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
Assuntos
Anti-Inflamatórios não Esteroides , Disponibilidade Biológica , Proteínas Sanguíneas , Oncorhynchus mykiss , ortoaminobenzoatos , Animais , Oncorhynchus mykiss/metabolismo , Oncorhynchus mykiss/sangue , ortoaminobenzoatos/farmacocinética , ortoaminobenzoatos/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/sangue , Administração Oral , Proteínas Sanguíneas/metabolismo , Injeções Intramusculares/veterinária , Ligação Proteica , Injeções Intravenosas/veterinária , Meia-VidaRESUMO
Here, it has been described that normal fresh sera from rainbow trout (oncorhynchus mykiss) were able to Iyse Tylodlphys sp. metacercariae isolated form Galaxias maculatus (Jenyns, 1842) (Teleostei, Galaxiidae) brain. This effect was time dependent, and progressively increased since 1 h up to 18 h incubation. There were oscillations in the ability of different sera samples to lyse these parasites. Similar values were achieved with other salmonid sera, and also with normal human sera pool. The lytic activity was abolished by heat-inactivated sera, by zymosan treatment and by incubation in the presence of EDTA. However, the mean values obtained in the presence of EGTA-Mg++ did not significantly differ from those found with sera as a source of complement. The results of this study suggested the role of complement alternative pathway on Tylodephys sp. in vitro lysis, under our experimental conditions
Assuntos
Animais , Cérebro/parasitologia , Técnicas In Vitro , Nematoides/patogenicidade , Oncorhynchus mykiss/parasitologia , Técnicas de Cultura de Células , Proteínas do Sistema Complemento/imunologia , Soros Imunes , Nematoides/isolamento & purificação , Oncorhynchus mykiss/sangue , Oncorhynchus mykiss/imunologia , Parasitemia/imunologiaRESUMO
Thirty-five normal, adult specimens of the rainbow trout Oncorhynchus mykiss (Richardson, 1836) cultured in the Neusa Fishculture Station (73 degrees 38'28r W; 5 degrees 8'30r N) were studied to establish normal blood values; the hematopoietic tissues (pronefros, spleen and thymus), and other organs such as the stomach were also structurally studied. The rainbow trout collected in the second half of 1990 and the beginning of the first half of 1991 had 1,415,000 erythrocytes and 22,000 leukocytes per mm3 of blood. Their hemoglobin concentration was 6.99 g/100ml. They had three types of circulating leukocytes: lymphorytes 65 per cent, polimorphonuclears 24 per cent and monocytes 11 per cent. The pronephros is the major hematopoietic organ in the rainbow trout. It produces mainly the polimorphonuclears; the spleen and the thymus are linfopoietics. The study of the hemocytometric values in the peripheral blood frotis and the structure of the hematopoietic organs of the rainbow trout is very useful, accessible and inexpensive. It produces data which yield information about physiological and pathological conditions