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1.
Einstein (Sao Paulo) ; 18: eAO4876, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576909

RESUMO

OBJECTIVE: To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. METHODS: Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. RESULTS: Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. CONCLUSION: Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Sericinas/uso terapêutico , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/análise , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Fígado Gorduroso/patologia , Trânsito Gastrointestinal/efeitos dos fármacos , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/fisiopatologia , Reprodutibilidade dos Testes , Sericinas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/análise , Ganho de Peso/efeitos dos fármacos
2.
Chemosphere ; 238: 124609, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524604

RESUMO

Human pharmaceuticals are pollutants of special concern due to their widespread consumption over the last decades, their high persistence in the environment, and the reported alterations produced on non-target organism. The antidepressant fluoxetine (FLX) exerts its effect by inhibiting serotonin (5-HT) reuptake at the presynaptic membrane, thus increasing brain serotonergic activity. In vertebrates, there is a clear inverse relationship between hypothalamic 5-HT levels and food intake, therefore we hypothesized that FLX would inhibit food intake, and in consequence alter energy metabolism in freshwater fish. The aim of this study was to analyze the effect of FLX on feeding behavior and energy storage of the cichlid fish Cichlasoma dimerus. Adult fish were intraperitoneally injected daily with 2 or 20 µg.g-1 FLX or saline for a 5-day period, during which the 20 µg.g-1 FLX-injected fish exhibited a marked reduction in food intake, consistent with a decrease in total body weight and total hepatocyte area observed at the end of the experiment. Although not statistically significant, a marked 50% decrease in glycogen and lipid content and an increase in protein levels in liver was observed for the 20 µg.g-1 FLX dose. This was evidenced histochemically by a weak PAS positive reaction and an intense Coomasie Blue stain. Taken together, these results suggest that the SSRI antidepressant FLX produces an anorectic effect in adults of C. dimerus, which could alter normal physiological function and, in consequence, have a negative impact on fish growth, reproduction, and population success.


Assuntos
Ciclídeos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Fluoxetina/toxicidade , Inibidores de Captação de Serotonina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Fígado/metabolismo , Masculino , Reprodução/efeitos dos fármacos
3.
Ecotoxicol Environ Saf ; 188: 109853, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704318

RESUMO

Nanoplastics (NPs) have become one of the most serious environmental problems nowadays. The environmental issues linked to NPs are attributed to the effects after ingestion in marine organisms. Due to the incipient and controversial information about the effects of PS NPs on the feeding of organisms, the aim of this work is to assess (i) digestion dynamics of Artemia franciscana when exposed to PS NPs as the lowest concentration of PS NPs reported in toxicity test [0 (control), 0.006 and 0.6 mg·L-1] and possible interferences in the ingestion of microalgae and (ii) the accumulation and depuration of PS NPs by A. franciscana. Artemia were subjected to ingestion experiments [24 h and 3.5 h], in which the organisms were exposed to PS NPs or to PS NPs + microalgae. Post-exposure feeding (24 h exposure and 2 h feeding) and depuration (24 h exposure and 24 h of depuration) were also carried out. More than 90% of the PS NPs were ingested by Artemia and bioaccumulated in the mandible, stomach, gut, tail gut and appendages after 24 h. The ingestion of microalgae was not affected by the presence of the PS NPs. Data of post-exposure feeding indicated that Artemia previously exposed to plastic and/or microalgae presented similar microalgal ingestion (around 70%); the highest microalgal consumption (around 90%) was recorded in the treatment in which Artemia were previously starved (no plastic and no microalgae). The presence of PS NPs in the gut after the depuration experiments indicates that 24 h was not enough to eliminate the PS NPs.


Assuntos
Artemia/efeitos dos fármacos , Artemia/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , /toxicidade , Poliestirenos/metabolismo , Poliestirenos/toxicidade , Animais , Artemia/metabolismo , Bioacumulação , Microalgas , Testes de Toxicidade , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
4.
J Agric Food Chem ; 67(49): 13737-13750, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31789024

RESUMO

Genistein is abundant in animal feed. In this study, the side effects of high-dose genistein on intestinal health and hypothalamic RNA profile were evaluated. Chicks exposed to high-dose genistein by intraperitoneal injection (416 ± 21, 34.5 ± 2.5) and feed supplementation (308 ± 19, 27.2 ± 2.1) both showed a reduced body weight gain and feed intake in comparison with the control group (261 ± 16, 22.7 ± 1.6, P < 0.01). In comparison with the control (22.4 ± 0.5, 33.3 ± 2.4), serum levels of albumin and total protein were decreased after high-dose genistein injection (21.6 ± 0.5, 31.8 ± 1.6) and diet supplementation (20.6 ± 0.9, 29.9 ± 2.5, P < 0.001). Interestingly, the genistein diet presented the chick hypothalamus with downregulated expression of bitter receptors (TAS1R3, P < 0.05). Meanwhile, it upregulated the expressions of TAS2R1 (P < 0.05) and downstream genes (PLCB2 and IP3R3) in the ileum (P < 0.05). Accordingly, high-dose dietary genistein reduced villus height and the abundance of Lactobacillus, along with the increased abundance of pathogenic bacteria in the ileum (P < 0.05). Furthermore, transcriptomic analysis identified 348 differently expressed genes (168 upregulated and 224 downregulated) in the high-dose dietary genistein treated group in comparison with the control (P < 0.05, |log2FoldChange| > 0.585). Therefore, high-dose dietary genistein altered the hypothalamic RNA profile and signal processing. Cluster analysis further revealed that high-dose dietary genistein significantly influenced apoptosis, the immune process, and the whole synthesis of steroid hormones in the hypothalamus (P < 0.05). In conclusion, high-dose dietary genistein altered the hypothalamic RNA profile and intestinal health of female chicks.


Assuntos
Galinhas/metabolismo , Suplementos Nutricionais/efeitos adversos , Genisteína/efeitos adversos , Hipotálamo/metabolismo , RNA/genética , Ração Animal/efeitos adversos , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Genisteína/análise , Hipotálamo/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/metabolismo , RNA/metabolismo , Esteroides/metabolismo
5.
Nat Commun ; 10(1): 4682, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615993

RESUMO

A priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia that limit quality and quantity of life. We demonstrate that TLR7/8 agonist R848 induces anti-tumor responses and attenuates cachexia in murine models of pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two of three cell lines were R848-sensitive, resulting in smaller tumor mass, increased immune complexity, increased CD8+ T-cell infiltration and activity, and decreased Treg frequency. R848-treated mice demonstrated improvements in behavioral and molecular cachexia manifestations, resulting in a near-doubling of survival duration. Knockout mouse studies revealed that stromal, not neoplastic, TLR7 is requisite for R848-mediated responses. In patient samples, we found Tlr7 is ubiquitously expressed in stroma across all stages of pancreatic neoplasia, but epithelial Tlr7 expression is relatively uncommon. These studies indicate immune-enhancing approaches including R848 may be useful in PDAC and cancer-associated cachexia.


Assuntos
Caquexia , Carcinoma Ductal Pancreático/metabolismo , Imidazóis/farmacologia , Neoplasias Intraductais Pancreáticas/metabolismo , Neoplasias Pancreáticas/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Ingestão de Alimentos/efeitos dos fármacos , Expressão Gênica , Humanos , Locomoção/efeitos dos fármacos , Camundongos , Camundongos Knockout , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Análise de Sequência de RNA , Taxa de Sobrevida , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/agonistas , Carga Tumoral , Microambiente Tumoral/imunologia
6.
Cell Physiol Biochem ; 53(4): 701-712, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592599

RESUMO

BACKGROUND/AIMS: Cholinergic signalling mediated by the activation of muscarinic and nicotinic receptors has been described in the literature as a classic and important signalling pathway in the regulation of the inflammatory response. Recent research has investigated the role of acetylcholine, the physiological agonist of these receptors, in the control of energy homeostasis at the central level. Studies have shown that mice that do not express acetylcholine in brain regions regulating energy homeostasis present with excessive weight gain and hyperphagia. However, it has not yet been well-described in the literature which cholinergic receptor subunits are involved in this response; moreover, the signalling pathways responsible for the observed effects are not fully delineated. The hypothalamus is the regulating centre of energy homeostasis, and the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is highly expressed in this region. When active, α7nAChR recruits proteins such as JAK2/STAT3 to mediate its signalling; the same intracellular components are required by leptin, an anorexigenic hormone. The aim of the present study was to evaluate the role of the hypothalamic α7nAChR in the control of energy homeostasis. METHODS: The work was performed on Swiss male mice. Initially, using immunofluorescent staining on brain sections, the presence of α7nAChR in hypothalamic cells regulating energy homeostasis was evaluated. Animals were submitted to stereotaxis in the lateral ventricle and intracerebroventricular stimulation (ICV) was used for the administration of an agonist (PNU) or antagonist (α-bungarotoxin) of α7nAChR. Metabolic parameters were evaluated and the expression of neuropeptides was evaluated in the hypothalamus by real-time PCR and western blot. The expression of hypothalamic neuropeptides was evaluated in mice treated with siRNA or inhibitors of JAK2/STAT3 (AG490 and STATTIC) proteins. We also evaluated food intake in α7nAChR knockout animals (α7KO). Additionally, in mouse hypothalamic cell culture (the mypHoA-POMC/GFP lineage), we evaluated the expression of neuropeptides and pSTAT3 after stimulation with PNU. RESULTS: Our results indicate co-localisation of α7nAChR with α-MSH, AgRP and NPY in hypothalamic cells. Pharmacological activation of α7nAChR reduced food intake and increased hypothalamic POMC expression and decreased NPY and AgRP mRNA levels and the protein content of pAMPK. Inhibition of α7nAChR with an antagonist increased the mRNA content of NPY and AgRP. Inhibition of α7nAChR with siRNA led to the suppression of POMC expression and an increase in AgRP mRNA levels. α7KO mice showed no changes in food intake. Inhibition of proteins involved in the JAK2/STAT3 signalling pathway reversed the effects observed after PNU stimulation. POMC-GFP cells, when treated with PNU, showed increased POMC expression and nuclear translocation of pSTAT3. CONCLUSION: Thus, selective activation of α7nAChR is able to modulate important markers of the response to food intake, suggesting that α7nAChR activation can suppress the expression of orexigenic markers and favour the expression of anorexics using the intracellular JAK2/STAT3 machinery.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Janus Quinase 2/metabolismo , Pró-Opiomelanocortina/metabolismo , Fator de Transcrição STAT3/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Proteína Relacionada com Agouti/genética , Animais , Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Bungarotoxinas/farmacologia , Linhagem Celular , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Pró-Opiomelanocortina/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Receptor Nicotínico de Acetilcolina alfa7/genética
7.
Endocrinology ; 160(12): 2787-2799, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593246

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months. Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, Lira did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats. In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hiperandrogenismo/complicações , Liraglutida/uso terapêutico , Síndrome Metabólica/prevenção & controle , Síndrome do Ovário Policístico/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Resistência à Insulina , Leptina/sangue , Lipídeos/sangue , Liraglutida/farmacologia , Síndrome Metabólica/etiologia , Pós-Menopausa , Distribuição Aleatória , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos
8.
Life Sci ; 235: 116858, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505195

RESUMO

AIMS: The current study was conducted to investigate the potential protective effects of hesperidin and its possible mechanisms of action on pancreatic ß-cells in diabetes. MAIN METHODS: Male Sprague Dawley rats were made diabetic using 65 mg/kg intraperitoneal injection of streptozotocin, and then administered daily with 100 mg/kg of hesperidin over 4 weeks. On conclusion of the experiment, blood and pancreatic tissue were collected to determine the function of ß-cells, apoptosis, oxidative stress, ER stress, and inflammation. KEY FINDINGS: Treatment of diabetic rats with hesperidin, significantly decreased fasting blood glucose and food intake, along with increased body weight, serum and pancreatic insulin levels, and pancreatic-duodenal homeobox-1 (PDX-1) protein expression. The beneficial roles of hesperidin on diabetic pancreatic ß-cells exhibited an increment in antioxidant SOD and GPx activities, and a decrement in nitrotyrosine as well as malondialdehyde (MDA) levels. Additionally, the elevated concentration of TNF-α and expressions of ER stress maker GRP78 and CHOP proteins in the pancreas of diabetic rats were significantly diminished by hesperidin treatment. Furthermore, hesperidin effectively modulated expressions of apoptosis-regulatory proteins in diabetic rat pancreas, as revealed by upregulating anti-apoptotic Bcl-xL; with a concomitant downregulating pro-apoptotic Bax, cleaved caspase-3, and inhibiting the activation of DNA repair protein poly (ADP-ribose) polymerase (PARP). SIGNIFICANCE: Collectively, these findings suggest that hesperidin may have the potential to protect pancreatic ß-cells and improve their function by suppressing oxidative and ER stress, along with activating its antioxidant, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hesperidina/farmacologia , Células Secretoras de Insulina/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Homeodomínio/biossíntese , Inflamação , Insulina/sangue , Insulina/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Superóxido Dismutase/metabolismo , Transativadores/biossíntese , Fator de Transcrição CHOP/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
9.
J Dairy Sci ; 102(11): 10340-10359, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495618

RESUMO

We have shown in 2 independent studies that cows who received recombinant bovine interleukin-8 (rbIL-8) administered intrauterinely shortly after parturition have a significant and long-lasting increase in milk yield. In the present study, we hypothesized that the increased milk production associated with rbIL-8 treatment is a consequence of increased postpartum dry matter intake (DMI) and orchestrated homeorhetic changes that prioritize milk production. Cows were enrolled into 1 of 3 treatment groups: those assigned to the control group (CTR; n = 70) received an intrauterine (IU) administration of 500 mL of Dulbecco's phosphate-buffered saline (DPBS) solution and 1 mL of DPBS solution intravenously (IV; jugular vein), those assigned to the rbIL-8 IV group (rbIL8-IV, n = 70) received an IV injection of 167 µg of rbIL-8 and 500 mL of DPBS solution IU, and cows assigned to the rbIL-8 IU group (rbIL8-IU, n = 70) received an IU administration with 1,195 µg of rbIL-8 diluted in 499.5 mL of DPBS solution and 1 mL of DPBS solution IV. Animals were housed in a tiestall from calving to 30 d in milk (DIM) to measure DMI. Blood samples were collected daily from calving to 7 DIM and weekly until 28 DIM. Insulin resistance was evaluated using an intravenous glucose tolerance test and intravenous insulin challenge test (IVICT) in a subgroup of cows (n = 20/treatment) at 10 and 11 DIM, respectively. Additionally, liver biopsy samples were taken at 14 DIM from the same subgroup of cows to measure triglyceride levels and cell proliferation and apoptosis. Cows treated with rbIL8-IU produced more milk (CTR = 36.9 ± 1.5; rbIL8-IU = 38.5 ± 1.5; rbIL8-IV = 36.6 ± 1.5 kg/d), energy-corrected milk (CTR = 42.9 ± 0.9; rbIL8-IU = 46.1 ± 0.8; rbIL8-IV = 43.7 ± 0.9 kg/d), and fat-corrected milk (CTR = 44.3 ± 0.9; rbIL8-IU = 47.8 ± 0.9; rbIL8-IV = 45.2 ± 0.9 kg/d) yields when compared with CTR cows, and no differences were observed between rbIL8-IV and CTR cows. The administration of rbIL8-IU significantly increased DMI compared with CTR (CTR = 18.8 ± 0.3; rbIL8-IU = 19.9 ± 0.3; rbIL8-IV = 19.3 ± 0.3 kg/d). Recombinant bIL-8 treatment did not affect glucose, insulin, or fatty acids (i.e., IVICT only) concentrations or their area under the curve in response to an intravenous glucose tolerance test and IVICT when compared with CTR. Moreover, rbIL-8 treatment administered IU or IV increased liver triglyceride levels. Additionally, cows treated with rbIL8-IU tended to have lower odds of developing hyperketonemia (odds ratio = 0.46, 95% confidence interval: 0.19 to 1.10), lower odds of clinical ketosis and displaced abomasum combined (odds ratio = 0.17, 95% confidence interval: 0.03 to 0.89), and lower odds of diseases combined (odds ratio = 0.43, 95% confidence interval: 0.21 to 0.86) when compared with CTR. We conclude that the administration of rbIL8-IU increases DMI, milk production, fat-corrected milk, and energy-corrected milk while improving overall health during the postpartum period. This study supports the use of rbIL-8 administered IU shortly after calving to improve health and production responses in lactating cows.


Assuntos
Bovinos/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , Resistência à Insulina , Interleucina-8/administração & dosagem , Lactação/efeitos dos fármacos , Ácido 3-Hidroxibutírico/sangue , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dieta/veterinária , Ácidos Graxos/metabolismo , Feminino , Glucose/metabolismo , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Insulina/sangue , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Cetose/veterinária , Lactação/fisiologia , Fígado/citologia , Fígado/efeitos dos fármacos , Leite/metabolismo , Parto , Período Pós-Parto/sangue , Gravidez , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia
10.
Biol Pharm Bull ; 42(9): 1554-1561, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474715

RESUMO

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of liver type phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Obesidade/prevenção & controle , Fenilbutiratos/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Animais , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Fluordesoxiglucose F18 , Glucose/metabolismo , Teste de Tolerância a Glucose , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Fenilbutiratos/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Ganho de Peso/efeitos dos fármacos
11.
Sheng Li Xue Bao ; 71(4): 514-526, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31440748

RESUMO

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated. In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 µg/kg), Exenatide (10 µg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities.


Assuntos
Ingestão de Alimentos/efeitos dos fármacos , Exenatida/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Liraglutida/farmacologia , Animais , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
12.
J Therm Biol ; 84: 164-175, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31466750

RESUMO

This study was conducted to investigate the effects of dietary GABA supplementation on blood biochemical parameters, the overall growth performance, and the relative mRNA expression of some FI- regulating genes in broiler chickens. A total of 192, three-day old chicks of mixed sex from two commercial broiler strains (Ross 308 and Cobb 500) were distributed into 2 groups; a control group and GABA-supplemented group (100 mg/kg diet). When the chicks reached 21 days of age, each group of each strain was randomly subdivided into two subgroups: one was exposed to HS (33 ±â€¯2 °C for 5 h/day for 2 weeks), while the other remained at thermoneutral temperature (24 °C). GABA significantly improved bird growth performance under normal and HS conditions, by increasing body weight (BW), weight gain (WG), and FI and significantly reduced the elevated body temperature of birds under HS. GABA supplementation increased FI by reducing the mRNA expression levels of FI-inhibiting neuropeptides, such as POMC, leptin, Ghrelin, and CCK, during HS and by increasing the expression of FI-stimulating neuropeptides such as AgRP and NPY. Moreover, GABA significantly altered FAS and ACC gene expression, resulting in significant increases in abdominal fat content in birds reared normally. In contrast, GABA lowered fat content in Cobb birds and increased it in Ross birds under HS. Therefore, GABA (100 mg/kg diet) is a strong FI-stimulating neurotransmitter and its regulatory effects depend on broiler strain and housing temperature.


Assuntos
Galinhas/fisiologia , Suplementos Nutricionais , Ingestão de Alimentos/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologia , Animais , Dieta/veterinária , Feminino , Transtornos de Estresse por Calor/metabolismo , Transtornos de Estresse por Calor/veterinária , Hormônios/genética , Abrigo para Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Doenças das Aves Domésticas/metabolismo , Temperatura Ambiente
13.
Food Chem Toxicol ; 133: 110751, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31390532

RESUMO

Chronic exposure to cadmium (Cd) causes remarkable damage to the liver and gastrointestinal tract. Previous studies have revealed that chlorogenic acid (CGA) could improve the intestinal barrier integrity for weaned rats. Hence, this study sought to investigate the protective effects of CGA from pure reagent and sunflower seed extract (SSE) on growth performance, antioxidant indicators, inflammatory biomarkers and intestinal barrier function in Cd treated rats. A total of 32 Sprague-Dawley female rats with similar weights were randomly allotted to four treatments: control, CdCl2 (6 mg/kg BW), co-treatment of Cd (6 mg/kg BW) and pure CGA (50 mg/kg BW), and co-treatment of Cd (6 mg/kg BW) and SSE (50 mg/kg BW) for 14 days. The data indicated that, CGA or SSE with Cd sequestration and good antioxidative ability decreased Cd absorption and accumulation in the jejunum and increased fecal Cd levels in Cd-exposed rats. Compared with the Cd group, co-treatment with CGA or SSE also alleviated inflammation, ameliorated the villus damage, reversed the disruption of tight junctions, and recovered weight gain of rats. These results suggest that CGA or SSE can protect the intestinal barrier, which is related to the alleviation of Cd-induced oxidative stress and growth decrease.


Assuntos
Ácido Clorogênico/farmacologia , Enteropatias/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Cádmio , Proteínas de Transporte de Cátions/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Enteropatias/induzido quimicamente , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Jejuno/efeitos dos fármacos , Jejuno/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley
14.
Lipids Health Dis ; 18(1): 157, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351498

RESUMO

BACKGROUND: The hypolipidemic effect of phytosterols has been wildely recognized, but its application is limited due to its insolubility in water and low solubility in oil. In this study, ß-sitosterol ester with linoleic acids and ß-sitosterol self-microemulsions were prepared and their hypolipidemic effects on hyperlipidemia mice were studied. METHODS: Firstly, the mice were randomly divided into normal group and model group,they were fed with basic diet and high-fat diet for 70 days respectively. After high-fat model mice was successfully established, the model group was further divided into eight groups: HFD (high-fat diet feeding), SELA-TSO(8 ml/kg, SELA:700 mg/kg), TSO (8 ml/kg), SSSM (8 ml/kg,SS:700 mg/kg), NLSM (8 ml/kg), SSHT-TSO (8 ml/kg, SS: 700 mg/kg) and SS-TSO (8 ml/kg, SS: 700 mg/kg) groups, and treated with ß-sitosterol ester with linoleic acid, ß-sitosterol self-microemulsion, commercial ß-sitosterol health tablets and ß-sitosterol powder for 35 days, respectively, and blank control groups were established. At the end of the treatment period, the blood lipid level, tissues, cholesterol and lipids in feces of mice in each group were investigated. Statistical and analytical data with SPSS 17.0 Software,statistical significance was set at p* < 0.05 and p** < 0.01 levels . RESULTS: The order of lowering blood lipid effect is listed as: SSSM> SELA-TSO > SSHT-TSO > SS-TSO, which shows that ß-sitosterolself-microemulsion have the highest treatment effect among the experimental groups. CONCLUSIONS: In this study, a new formulation of ß-sitosterol was developed, and its hypolipidemic effect was investigated. The results showed that ß-sitosterol self-microemulsion has a good blood lipid lowering effect.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Ácido Linoleico/farmacologia , Sitosteroides/farmacologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/administração & dosagem , Emulsões/química , Emulsões/farmacologia , Fezes/química , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hipolipemiantes/administração & dosagem , Hipolipemiantes/química , Ácido Linoleico/administração & dosagem , Ácido Linoleico/química , Lipídeos/sangue , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho do Órgão/efeitos dos fármacos , Sitosteroides/administração & dosagem , Sitosteroides/química , Comprimidos/administração & dosagem , Comprimidos/farmacologia
15.
Life Sci ; 232: 116672, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31336120

RESUMO

AIMS: Obesity is not only associated with metabolic diseases but is also a symptom of menopause in women. To date, there are no effective drugs for the management of obesity, and it is important to find new agents with fewer side effects, for the treatment of obesity. This study aimed to determine the anti-obesity effect of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, and its underlying mechanism in rats with ovariectomy-induced obesity. MAIN METHODS: Ovariectomy (Ovx) rats were treated with 17-DMAG (1 mg kg-1, intraperitoneally) for eight weeks from one week after surgery. The body weight, food intake, locomotor activity, adipogenic- and autophagy-related protein expression in white adipose tissue (WAT) and plasma triglyceride (TG) levels were measured in sham and Ovx rats. KEY FINDINGS: Compared with sham rats, Ovx rats showed increased weight gain, food intake, WAT mass, TG levels, adipogenic protein expression, and decreased locomotor activity. Furthermore, autophagy-related proteins and Foxo3a of WAT were significantly increased in Ovx rats. However, with the exclusion of increased food intake, the changes induced by Ovx were all reversed in 17-DMAG-treated Ovx rats. In addition, the expression of Hsp70 and phosphorylation of Akt increased in 17-DMAG-treated Ovx rats. SIGNIFICANCE: These results suggest that 17-DMAG significantly ameliorated obesity induced by Ovx, and this phenomenon is accompanied by the downregulation of adipogenic-related and autophagy-related proteins as well as the upregulation of Akt-phosphorylation and Hsp70 expression. Therefore, 17-DMAG may be a potential agent for preventing or treating obesity in postmenopausal women.


Assuntos
Benzoquinonas/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Lactamas Macrocíclicas/farmacologia , Obesidade/etiologia , Obesidade/prevenção & controle , Ovariectomia/efeitos adversos , Adipogenia , Tecido Adiposo/metabolismo , Animais , Autofagia , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Proteínas de Choque Térmico HSP90/metabolismo , Locomoção/efeitos dos fármacos , Ratos
16.
Amino Acids ; 51(8): 1129-1152, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302780

RESUMO

Animals at the neonatal stage have to eat more to support better growth and health. However, it is difficult to understand the mechanism of feeding during an early stage of life in the brain of the rodent model. Chickens are precocial and they can look for their food by themselves right after hatching. Neonatal chicks have a relatively large-sized brain; therefore, the drugs are easy to administer centrally and changes in food intake can be clearly monitored. Sleeping status, which affects food intake, can be estimated from the posture. The closest vertebrate outgroup to mammals is birds, but it was reported that the organization of the human genome is closer to that of the chicken than the mouse. Thus, it is important to understand the central mechanism of feeding regulation in the neonatal chicks. In neuropeptides, the number of candidates as the orexigenic factor was less than those as the anorexigenic factor, even at an early growth stage. Some of the neuropeptides have reverse effects, e.g., ghrelin and prolactin releasing peptides, or no effects compared to the effects confirmed in mammals. Some of the genetic differences between meat-type (broiler) and layer-type chickens would explain the difference in food intake. On the other hand, it was difficult to explain the feeding mechanism by neuropeptides alone, as neonatal chicks have a repeated feeding, sleeping, and resting behavior within a short period. Some of the amino acids and their metabolites act centrally to regulate feeding with sedative and hypnotic effects. In conclusion, endogenous neuropeptides and endogenous and/or exogenous nutrients like amino acids collaborate to regulate feeding behavior in neonatal chicks.


Assuntos
Aminoácidos/farmacologia , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Neuropeptídeos/farmacologia , Animais , Animais Recém-Nascidos , Galinhas , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos
17.
Pak J Pharm Sci ; 32(3): 899-903, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278697

RESUMO

Methylphenidate (MPD), a psycho-stimulant is a prescription medicine for the treatment of Attention deficit hyperactivity disorder (ADHD). The drug is also being increasingly used by general population for enhancing cognition. Only few preclinical studies have been carried out on the effects of MPD on cognition and these studies show either an enhancement or impairment of memory following the administration of MPD. The present study was designed to evaluate the effects of different doses of methylphenidate on acquisition and retention of memory in Morris water-maze test. Twenty four male Albino Wistar rats (weighing 180-220gm) were randomly assigned to four groups: (1) Control (2) 0.5mg/kg (3) 2.5mg/kg (4) 5 mg/kg methylphenidate. Animals received drug or water orally before training phase. Memory acquisition was monitored 2hrs post drug administration while memory retention was determined next day. It was found that the clinically relevant doses of methylphenidate (0.5mg/kg and 2.5mg/kg) improved memory acquisition and its retention but higher dose (5mg/kg) impaired both. We suggest that MPD-induced increase of catecholamine neurotransmission may have a role in the improvement of water maze performance while agonist activity of the drug for 5HT-1A receptor in the impaired performance at high doses. Food intake and body weight changes were not affected by MPD administration due to short-term administration of the drug. Results may help in improving pharmaco-therapeutic use of MPD for ADHD.


Assuntos
Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilfenidato/administração & dosagem , Metilfenidato/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/farmacologia , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Metilfenidato/efeitos adversos , Ratos Wistar
18.
J Vet Intern Med ; 33(4): 1619-1626, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31268578

RESUMO

BACKGROUND: Synbiotics decrease antibiotic-associated gastrointestinal signs (AAGS) in cats, but data supporting synbiotic use to ameliorate AAGS in dogs are lacking. OBJECTIVES: To determine if administration of synbiotics mitigates AAGS in dogs. ANIMALS: Twenty-two healthy research dogs. METHODS: Randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study with an 8-week washout period. Each period included a 1-week baseline and 3-week treatment phase. Dogs received enrofloxacin (10 mg/kg PO q24h) and metronidazole (12.5 mg/kg PO q12h), followed 1 hour later by a bacterial/yeast synbiotic combination or placebo. Food intake, vomiting, and fecal score were compared using repeated-measures crossover analyses, with P < .05 considered significant. RESULTS: Hyporexia, vomiting, and diarrhea occurred in 41% (95% confidence interval [CI], 21-64), 77% (95% CI, 55-92), and 100% (95% CI, 85-100) of dogs, respectively, during the first treatment period. Derangements in food intake were smaller in both periods for dogs receiving synbiotics (F-value, 5.1; P = .04) with treatment-by-period interactions (F-value, 6.0; P = .02). Days of vomiting differed over time (F-value, 4.7; P = .006). Fecal scores increased over time (F-value, 33.5; P < .001), were lower during period 2 (F-value, 14.5; P = .001), and had treatment-by-period effects (F-value, 4.8; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Enrofloxacin/metronidazole administration is associated with a high frequency of AAGS. Synbiotic administration decreases food intake derangements. The presence of milder AAGS in period 2 suggests that clinical effects of synbiotics persist >9 weeks after discontinuation, mitigating AAGS in dogs being treated with antibiotics followed by placebo.


Assuntos
Antibacterianos/efeitos adversos , Doenças do Cão/induzido quimicamente , Enrofloxacina/efeitos adversos , Gastroenteropatias/veterinária , Metronidazol/efeitos adversos , Simbióticos/administração & dosagem , Vômito/induzido quimicamente , Animais , Estudos Cross-Over , Doenças do Cão/prevenção & controle , Cães , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Masculino , Distribuição Aleatória , Vômito/prevenção & controle , Vômito/veterinária
19.
BMC Complement Altern Med ; 19(1): 166, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286942

RESUMO

BACKGROUND: To evaluate the pharmaceutical safety of Myelophil, an ethanol extract of a mixture of Astragali Radix and Salviae Miltiorrhizae Radix, using both acute and repeated toxicological studies. METHODS: A total of 40 beagle dogs (20 each male and female) were fed doses up to 5,000 mg/kg for the acute study and up to 1,250 mg/kg for the 13-week repeated dose toxicological study. Adverse effects were examined intensively by comparing the differences between normal and drug-administered groups using clinical signs, autopsies, histopathological findings, hematology, urinalysis, and biochemical analysis. RESULTS: No mortality or drug-related clinical signs were observed in the Myelophil-treated groups, except for vomiting due to an excessive dose (5,000 mg/kg). Likewise, in the repeated toxicity test, compound-colored stools in the Myelophil-treated groups and soft stools in all groups, including the control, were observed. No drug-related abnormalities were found in the histopathology, hematology, urinalysis, and biochemical analyses for any doses of Myelophil. CONCLUSION: These results support the safety of Myelophil with a no observed adverse effect level (NOAEL) of 1250 mg/kg in beagle dogs, which corresponds to a human equivalent dose (HED) of 694 g/kg.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Cães , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Testes de Toxicidade Aguda
20.
Neuropeptides ; 76: 101937, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31253440

RESUMO

The progesterone metabolite, allopregnanolone (AlloP), is a GABAA receptor modulating steroid and is known to have orexigenic and pro-obesity effects. The neurobiological mechanisms underpinning these effects are most likely due to enhanced GABAergic signaling in the lateral arcuate nucleus (ARC) and medial paraventricular nucleus (PVN) of the hypothalamus. Inspired by the finding that GABAergic signaling is also important for the orexigenic effects of the circulating hormone, ghrelin, we sought to determine the extent to which AlloP (one of the most potent endogenous GABAA-receptor modulators) operates alongside ghrelin to enhance food intake. Male rats with ad libitum access to standard chow were injected intravenously with AlloP and/or ghrelin, alone or in combination. The intake of the standard chow was greater after AlloP 1 mg/kg together with ghrelin 30 µg/kg than with 30 µg/kg ghrelin alone. Food intake was also increased for the combined treatment of AlloP 0.5 mg/kg + ghrelin 10 µg/kg, AlloP 1 mg/kg + ghrelin 10 µg/kg, and AlloP 0.5 mg/kg + ghrelin 30 µg/kg. There was no significant difference in food intake between the two ghrelin doses or between the two doses of AlloP and the vehicle. In electrophysiological studies, physiologically relevant concentrations of AlloP prolonged the current decay time of spontaneous inhibitory post-synaptic current of dissociated cells of the ARC and PVN. We conclude that AlloP enhances the hyperphagic effect of ghrelin, findings of potential relevance for the hyperphagia associated with the luteal phase of the reproductive cycle.


Assuntos
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Grelina/administração & dosagem , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Pregnanolona/administração & dosagem , Animais , Núcleo Arqueado do Hipotálamo/fisiologia , Grelina/fisiologia , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Masculino , Núcleo Hipotalâmico Paraventricular/fisiologia , Pregnanolona/fisiologia , Ratos Wistar
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