RESUMEN
Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.
Asunto(s)
Biotina , Restricción Calórica , Suplementos Dietéticos , Retardo del Crecimiento Fetal , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Embarazo , Ratas , Restricción Calórica/métodos , Biotina/administración & dosificación , Biotina/farmacología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Retardo del Crecimiento Fetal/prevención & control , Retardo del Crecimiento Fetal/etiología , Resistencia a la Insulina , Modelos Animales de Enfermedad , Síndrome Metabólico/prevención & control , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Fructosa/efectos adversos , Factores de Riesgo Cardiometabólico , Peso Corporal/efectos de los fármacos , Presión Sanguínea/efectos de los fármacosRESUMEN
The objectives of this experiment were to evaluate the effects of supplementation of Nellore (Bos indicus) cows with ß-carotene + vitamins A + D3 + E + biotin on body condition score (BCS), oestrus, pregnancy, and foetal morphometry. Lactating cows (n = 497) from two herds were balanced for BCS and calving period [early calving (EC); late calving (LC)] and were assigned randomly to: Control (n = 251)-supplementation with a mineral supplement; and SUP (n = 246)-supplementation with the mineral supplement fed to control + ß-carotene (150 mg/day) + vitamin A (40,000 IU/day) + vitamin D3 (5000 IU/day) + vitamin E (300 mg/day) + biotin (20 mg/day). Cows were supplemented from Days -30 to 30 (Day 0 = timed artificial insemination; TAI). Pregnancy was diagnosed 30 days after TAI and foetal crown-rump distance and thoracic diameter were measured at 30 and 77 days of gestation. Cows in the SUP treatment were more likely to have BCS ≥3.0 on Day 0 (63.0 ± 3.1 vs. 60.2 ± 3.1; p < .01) and were more likely to gain BCS from Days -30 to 30 (57.7 ± 3.3 vs. 44.1 ± 3.3%; p < .01). Fewer LC cows in the SUP treatment were detected in oestrus at the time of the first TAI (Control: LC: 75.4 ± 4.4 vs. SUP: LC: 64.0 ± 5.2 vs. Control: EC: 65.3 ± 4.0 vs. SUP: EC: 71.8 ± 3.7; p = .04). There was a tendency for the SUP treatment to increase pregnancy to the first TAI (64.2 ± 3.0 vs. 56.6 ± 3.1%; p = .08). A greater percentage of SUP cows was detected in oestrus at the time of the second TAI (70.1 ± 5.0 vs. 52.3 ± 4.8%; p = .01). The SUP treatment increased pregnancy to the second TAI among LC cows (SUP: LC: 75.9 ± 8.0% vs. Control: LC: 50.0 ± 8.3% vs. Control: EC: 52.0 ± 5.9% vs. SUP: EC: 41.4 ± 6.5%; p = .02). The SUP treatment increased foetal size (crown-rump; p = .04 and thoracic diameter; p < .01) at 30 days of gestation and, despite decreasing crow-rump length at 77 days after the first TAI among EC cows (p < .01), it increased the thoracic diameter at 77 days after the first TAI independent of calving season. Our results support that pregnancy establishment and foetal growth can be improved when grazing Nellore cows are supplemented with ß-carotene and vitamins A + D3 + E + biotin.
Asunto(s)
Biotina , Suplementos Dietéticos , Estro , Vitamina A , Vitamina E , beta Caroteno , Animales , Bovinos , Femenino , Embarazo , Vitamina A/administración & dosificación , Vitamina A/farmacología , beta Caroteno/administración & dosificación , beta Caroteno/farmacología , Vitamina E/administración & dosificación , Vitamina E/farmacología , Estro/efectos de los fármacos , Biotina/administración & dosificación , Biotina/farmacología , Colecalciferol/farmacología , Colecalciferol/administración & dosificación , Folículo Ovárico/efectos de los fármacos , Dieta/veterinaria , Vitaminas/administración & dosificación , Vitaminas/farmacología , Alimentación Animal , Lactancia , Feto/efectos de los fármacosAsunto(s)
Biotina , Estudios Cruzados , Cabello , Minoxidil , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Administración Oral , Administración Tópica , Alopecia/tratamiento farmacológico , Biotina/administración & dosificación , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Minoxidil/administración & dosificación , Resultado del TratamientoRESUMEN
The aim of this study was to evaluate the effect of daily biotin supplementation on the mineral composition and microstructure of the abaxial hoof wall in dairy heifers. The heifers were housed on a concrete floor and fed for weight gain more than 800 g per day, which is a challenging environment for the hoof. Twelve crossbred dairy heifers (Jersey × Holstein) were divided into two treatment groups. Animals in the control group (n = 6) received a diet without supplemental biotin, while the heifers in the biotin-supplemented feed group (n = 6) each received 20 mg of biotin daily for 120 days. Samples of the abaxial hoof wall were collected from the outer claw of the fore and hind limb, before and after supplementation. The samples were evaluated by X-ray fluorescence spectrometry, computed microtomography, atomic force microscopy and confocal laser scanning microscopy. Biotin supplementation increased the sulphur content and decreased the calcium and potassium content in the abaxial hoof wall. Biotin treatment also increased the percentage of horn tubules with smaller diameter marrow (17-51 µm). However, biotin did not influence the surface relief of the hoof wall, suggesting that its action is limited to the inner layers of the stratum corneum. Daily supplementation with 20 mg of biotin promoted changes in the mineral composition and microstructure of abaxial hoof wall of crossbred dairy heifers. These findings suggest biotin supplementation improves hoof quality and may help to understand the function of biotin in the stratum corneum.
Asunto(s)
Biotina/farmacología , Bovinos/fisiología , Suplementos Dietéticos , Pezuñas y Garras/química , Minerales/química , Complejo Vitamínico B/farmacología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Biotina/administración & dosificación , Dieta/veterinaria , Femenino , Minerales/metabolismo , Complejo Vitamínico B/administración & dosificación , Microtomografía por Rayos XRESUMEN
The objective of this study was to evaluate the effect of biotin supplementation on milk yield and the reproductive efficiency in Girolando cows. The study was conducted on a dairy farm located in central Brazil, between April 2012 and December 2016. Thirty-six Girolando cows in their first lactation were used. The cows were distributed in two treatment groups, each with equivalent weight distributions. Control treatment (CT) cows (n = 18) received a diet without any supplemental biotin, whereas biotin treatment (BT) cows (n = 18) received a diet supplemented with 20 mg/day of biotin during lactation. Biotin supplementation caused a significant increase (p = 0.001) in milk yield in the second lactation, and a trend (p = 0.09) toward higher average production during the three lactations was evaluated. There was no statistically significant difference between the treatments in terms of reproductive efficiency. In conclusion, biotin supplementation (20 mg/day) during lactation for Girolando cows reared in a tropical climate is able to increase milk yield, but does not improve reproductive efficiency.
Asunto(s)
Biotina/farmacología , Bovinos/fisiología , Lactancia/efectos de los fármacos , Leche , Clima Tropical , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Biotina/administración & dosificación , Brasil , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Reproducción/efectos de los fármacosRESUMEN
During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation. Biotin might have a potential action on islet maturation. Pharmacological concentrations of biotin have been found to modify islet morphology and function. In a previous study, we found that mice fed a biotin-supplemented diet for 8 weeks after weaning showed an increase in basal and glucose stimulated insulin secretion, enlarged islet size, and modified islet structure. In the present study, we investigated the effect of biotin on maturation features during the first week postweaning. Female BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 1 week after weaning. Compared with the control, biotin-supplemented mice showed an increase in pancreatic islet number and area in addition to an augmented proportion of beta-cells in the islet. These effects were related to an increase in beta-cell proliferation. No differences were found in insulin secretion, blood glucose concentrations, or serum insulin levels. These results indicate that biotin supplementation is capable of affecting beta-cell proliferation and might be a therapeutic agent for establishing strategies for regenerative medicine.
Asunto(s)
Biotina/administración & dosificación , Diferenciación Celular , Proliferación Celular , Suplementos Dietéticos , Células Secretoras de Insulina/citología , Islotes Pancreáticos/crecimiento & desarrollo , Complejo Vitamínico B/administración & dosificación , Animales , Apoptosis , Biotina/efectos adversos , Biotina/metabolismo , Biotina/uso terapéutico , Glucemia/análisis , Recuento de Células , Suplementos Dietéticos/efectos adversos , Femenino , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/citología , Islotes Pancreáticos/metabolismo , Ratones Endogámicos BALB C , Tamaño de los Órganos , Concentración Osmolar , Estado Prediabético/prevención & control , Distribución Aleatoria , Técnicas de Cultivo de Tejidos , Complejo Vitamínico B/efectos adversos , Complejo Vitamínico B/metabolismo , Complejo Vitamínico B/uso terapéutico , DesteteRESUMEN
OBJECTIVE: Despite increasing evidence that pharmacologic concentrations of biotin modify glucose metabolism, to our knowledge there have not been any studies addressing the effects of biotin supplementation on glucagon production and secretion, considering glucagon is one of the major hormones in maintaining glucose homeostasis. The aim of this study was to investigate the effects of dietary biotin supplementation on glucagon expression, secretion, and action. METHODS: Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg biotin/kg diet) for 8 wk postweaning. Glucagon gene mRNA expression was measured by the real-time polymerase chain reaction. Glucagon secretion was assessed in isolated islets and by glucagon concentration in plasma. Glucagon action was evaluated by glucagon tolerance tests, phosphoenolpyruvate carboxykinase (Pck1) mRNA expression, and glycogen degradation. RESULTS: Compared with the control group, glucagon mRNA and secretion were increased from the islets of the biotin-supplemented group. Fasting plasma glucagon levels were higher, but no differences between the groups were observed in nonfasting glucagon levels. Despite the elevated fasting glucagon levels, no differences were found in fasting blood glucose concentrations, fasting/fasting-refeeding glucagon tolerance tests, glycogen content and degradation, or mRNA expression of the hepatic gluconeogenic rate-limiting enzyme, Pck1. CONCLUSIONS: These results demonstrated that dietary biotin supplementation increased glucagon expression and secretion without affecting fasting blood glucose concentrations or glucagon tolerance and provided new insights into the effect of biotin supplementation on glucagon production and action.
Asunto(s)
Biotina/administración & dosificación , Glucagón/metabolismo , Glucagón/farmacología , Animales , Dieta , Suplementos Dietéticos , Expresión Génica/efectos de los fármacos , Glucagón/genética , Gluconeogénesis/efectos de los fármacos , Glucógeno/metabolismo , Islotes Pancreáticos/química , Islotes Pancreáticos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , ARN Mensajero/análisisRESUMEN
Several studies have shown that pharmacological concentrations of biotin decrease hyperlipidemia. The molecular mechanisms by which pharmacological concentrations of biotin modify lipid metabolism are largely unknown. Adipose tissue plays a central role in lipid homeostasis. In the present study, we analyzed the effects of biotin supplementation in adipose tissue on signaling pathways and critical proteins that regulate lipid metabolism, as well as on lipolysis. In addition, we assessed serum fatty acid concentrations. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (control: 1.76 mg biotin/kg; supplemented: 97.7 mg biotin/kg diet) over 8 weeks postweaning. Compared with the control group, biotin-supplemented mice showed an increase in the levels of adipose guanosine 3',5'-cyclic monophosphate (cGMP) (control: 30.3±3.27 pmol/g wet tissue; supplemented: 49.5±3.44 pmol/g wet tissue) and of phosphorylated forms of adenosine 5'-monophosphate-activated protein kinase (AMPK; 65.2%±1.06%), acetyl-coenzyme A (CoA), carboxylase-1 (196%±68%), and acetyl-CoA carboxylase-2 (78.1%±18%). Serum fatty acid concentrations were decreased (control: 1.12±0.04 mM; supplemented: 0.91±0.03 mM), and no change in lipolysis was found (control: 0.29±0.05 µmol/mL; supplemented: 0.33±0.08 µmol/mL). In conclusion, 8 weeks of dietary biotin supplementation increased adipose tissue cGMP content and protein expression of the active form of AMPK and of the inactive forms of acetyl-CoA carboxylase-1 and acetyl-CoA carboxylase-2. Serum fatty acid levels fell, and no change in lipolysis was observed. These findings provide insight into the effects of biotin supplementation on adipose tissue and support its use in the treatment of dyslipidemia.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo/química , Tejido Adiposo/metabolismo , Biotina/administración & dosificación , GMP Cíclico/análisis , Ácidos Grasos no Esterificados/sangre , Acetil-CoA Carboxilasa/análisis , Acetil-CoA Carboxilasa/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Suplementos Dietéticos , Activación Enzimática/efectos de los fármacos , Lipólisis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , FosforilaciónRESUMEN
Digital dermatitis can impair the health and milk yield of dairy cattle. Treatment of digital dermatitis involves corrective trimming and footbaths. The results of these are not always satisfactory, with na added risk of persisting residues in the dairy products and environment. In this study, we evaluated the effect of Stryphnodendron adstringens (Martius) Coville extract (applied via footbath or directly over the lesions) and biotin supplementation on wound healing in 90 surgically-corrected digital dermatitisaffected dairy cows. All animals were female, crossbred (Holstein × Gir), affected with digital dermatitis to different degrees of severity. The lesions were evaluated over a 45-day post-surgical period, and the cows were divided to six treatment groups. The groups were divided based on application of the extract as a footbath solution with or without supplemental biotin, application by brushing with or without biotin, and cleaning with water with or without biotin. The evaluation was performed considering the rates and recovery times. Supplementation with biotin did not influence the rate or recovery time of the surgical wounds. Topical application of the bark extract (via footbath solution and brushing) was determined to be more beneficial than washing with water.
A dermatite digital compromete a saúde e produtividade dos bovinos. O controle da enfermidade pode ser feito com a apara corretiva do casco e passagem dos animais em pedilúvio. Os resultados nem sempre são satisfatórios e há o risco de ocorrerem resíduos na carne, leite e no ambiente. No presente estudo avaliou-se a reparação de feridas cirúrgicas de dermatite digital após aplicação tópica do extrato da casca de barbatimão, em pedilúvio ou por pincelamento, e suplementação com biotina, em 90 vacas de aptidão leiteira. Todos os animais eram fêmeas, mestiças (Gir x Holandesa) e apresentavam dermatite digital em graus variados. As feridas foram analisadas em vários momentos durante 45 dias. Os animais foram divididos em seis grupos de 15 de acordo com o protocolo. Avaliou-se a aplicação do barbatimão em pedilúvio com ou sem suplementação de biotina, barbatimão por pincelamento com ou sem biotina e limpeza com água sob pressão com ou sem biotina, considerando os índices e os tempos de recuperação. A suplementação com biotina não influenciou os índices nem o tempo de recuperação das feridas cirúrgicas de dermatite digital e o uso tópico do extrato da casca do barbatimão, independente da forma de aplicação, se mostrou benéfico em relação à aplicação de água.
Asunto(s)
Animales , Bovinos , Biotina/administración & dosificación , Biotina/uso terapéutico , Dermatitis Digital/tratamiento farmacológico , Enfermedades de los Bovinos , Herida Quirúrgica/tratamiento farmacológico , Herida Quirúrgica/veterinaria , Stryphnodendron barbatimam/administración & dosificación , Stryphnodendron barbatimam/uso terapéuticoRESUMEN
Digital dermatitis can impair the health and milk yield of dairy cattle. Treatment of digital dermatitis involves corrective trimming and footbaths. The results of these are not always satisfactory, with na added risk of persisting residues in the dairy products and environment. In this study, we evaluated the effect of Stryphnodendron adstringens (Martius) Coville extract (applied via footbath or directly over the lesions) and biotin supplementation on wound healing in 90 surgically-corrected digital dermatitisaffected dairy cows. All animals were female, crossbred (Holstein × Gir), affected with digital dermatitis to different degrees of severity. The lesions were evaluated over a 45-day post-surgical period, and the cows were divided to six treatment groups. The groups were divided based on application of the extract as a footbath solution with or without supplemental biotin, application by brushing with or without biotin, and cleaning with water with or without biotin. The evaluation was performed considering the rates and recovery times. Supplementation with biotin did not influence the rate or recovery time of the surgical wounds. Topical application of the bark extract (via footbath solution and brushing) was determined to be more beneficial than washing with water.(AU)
A dermatite digital compromete a saúde e produtividade dos bovinos. O controle da enfermidade pode ser feito com a apara corretiva do casco e passagem dos animais em pedilúvio. Os resultados nem sempre são satisfatórios e há o risco de ocorrerem resíduos na carne, leite e no ambiente. No presente estudo avaliou-se a reparação de feridas cirúrgicas de dermatite digital após aplicação tópica do extrato da casca de barbatimão, em pedilúvio ou por pincelamento, e suplementação com biotina, em 90 vacas de aptidão leiteira. Todos os animais eram fêmeas, mestiças (Gir x Holandesa) e apresentavam dermatite digital em graus variados. As feridas foram analisadas em vários momentos durante 45 dias. Os animais foram divididos em seis grupos de 15 de acordo com o protocolo. Avaliou-se a aplicação do barbatimão em pedilúvio com ou sem suplementação de biotina, barbatimão por pincelamento com ou sem biotina e limpeza com água sob pressão com ou sem biotina, considerando os índices e os tempos de recuperação. A suplementação com biotina não influenciou os índices nem o tempo de recuperação das feridas cirúrgicas de dermatite digital e o uso tópico do extrato da casca do barbatimão, independente da forma de aplicação, se mostrou benéfico em relação à aplicação de água.(AU)
Asunto(s)
Animales , Bovinos , Stryphnodendron barbatimam/administración & dosificación , Stryphnodendron barbatimam/uso terapéutico , Biotina/administración & dosificación , Biotina/uso terapéutico , Enfermedades de los Bovinos , Herida Quirúrgica/tratamiento farmacológico , Herida Quirúrgica/veterinaria , Dermatitis Digital/tratamiento farmacológicoRESUMEN
The effects of orally administered biotin supplementation on the growth of claw horn in young, clinically healthy cattle were analyzed. Twelve, 1-year-old Girolando cattle were randomly assigned to receive either 12.5 mg of diluted powdered biotin (GI) or a control treatment (GII) for 40 consecutive days. Cattle in the GI group showed an average hoof growth of 11.3 +/- 0.72 mm, while those in GII had an average hoof growth of 7.2 +/- 0.78 mm. The results confirmed the positive effect of biotin supplementation on the growth of angle and length of the dorsal hoof wall, hoof sole length, and on resistance to wearing, in young cattle extensively managed.
Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Biotina/farmacología , Bovinos/crecimiento & desarrollo , Pezuñas y Garras/efectos de los fármacos , Pezuñas y Garras/crecimiento & desarrollo , Animales , Biotina/administración & dosificación , Enfermedades de los Bovinos/prevención & control , Suplementos Dietéticos , Enfermedades del Pie/prevención & control , Enfermedades del Pie/veterinaria , Masculino , Distribución AleatoriaRESUMEN
Besides its role as a carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. Several studies have shown that pharmacological concentrations of biotin reduce hypertriglyceridemia. The molecular mechanisms by which pharmacological concentrations of biotin affect lipid metabolism are largely unknown. The present study analyzed the effects of pharmacological doses of biotin on triglyceridemia, insulin sensitivity and on mRNA expression of various lipogenic genes. Three-week-old male BALB/cAnN Hsd mice were fed a biotin-control or a biotin-supplemented diet (1.76 or 97.7mg of free biotin/kg diet, respectively) over a period of eight weeks. Serum triglyceride concentrations, insulin and glucose tolerance and mRNA abundance of various lipogenic genes were investigated. The biotin-supplemented group showed 35% less serum triglycerides than control mice. In the liver, we found a significant (P<0.05) reduction of mRNA levels of SREBP1-c, glucose transporter-2, phosphofructokinase-1, pyruvate kinase, acetyl-CoA carboxylase and fatty acid synthase, while glucose-6-phosphate dehydrogenase expression increased. No changes in glucokinase, stearoyl-CoA desaturase-1, FoxO1 or PPAR-gamma expression were observed. In adipose tissue, we found a decreased expression of SREBP1c, glucose-6-phosphate deshydrogenase, acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, phosphofructokinase-1 and PPAR-gamma, but no changes in FoxO1 expression. Moreover, the group fed a biotin-supplemented diet showed a significant decrease in adipose tissue weight. No differences in insulin sensitivity or serum insulin concentrations were observed between groups. Our results indicate that pharmacological concentrations of biotin decrease serum tryglyceride concentrations and lipogenic gene expression in liver and adipose tissues.
Asunto(s)
Biotina/farmacología , Lipogénesis/efectos de los fármacos , Triglicéridos/sangre , Complejo Vitamínico B/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Biotina/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Resistencia a la Insulina , Lipogénesis/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/metabolismo , Complejo Vitamínico B/administración & dosificaciónRESUMEN
Biotin deficiency and biotin excess have both been found to affect reproduction and cause teratogenic effects. In the reproductive tract, however, the effects of biotin have not been well established yet. We investigated the effects of varying biotin content diets on the oestrus cycle, ovarian morphology, estradiol and progesterone serum levels, and the uterine mRNA abundance of their nuclear receptors, as well as on the activity of the estradiol-degrading group of enzymes cytochrome P450 (CYP) in the liver. Three-week-old female BALB/cAnN Hsd mice were fed a biotin-deficient, a biotin-control, or a biotin-supplemented diet (0, 7.2 or 400 micromol of free biotin/kg diet, respectively) over a period of nine weeks. Striking effects were observed in the biotin-deficient group: mice showed arrested estrous cycle on the day of diestrus and changes in ovary morphology. Estradiol serum concentration increased 49.2% in biotin-deficient mice compared to the control group, while the enzymatic activities of CYP1A2 and CYP2B2 increased (P<0.05). The mRNA abundance of nuclear estrogen and progesterone receptors decreased in the biotin-deficient mice. In the biotin-supplemented group we found that, in spite of a significant (P<0.05) decrease in the number of primary and Graafian follicles and in CYP1A2 activities, mice exhibited 105.4% higher serum estradiol concentration than the control group. No changes in the expression of the nuclear receptors were observed. No significant differences were observed in serum progesterone among the groups. Our results indicate that both the deficiency and the excess of biotin have significant effects on the female mouse reproductive system.
Asunto(s)
Biotina/deficiencia , Biotina/farmacología , Reproducción/efectos de los fármacos , Reproducción/fisiología , Animales , Biotina/administración & dosificación , Biotina/sangre , Peso Corporal/efectos de los fármacos , Dieta , Estradiol/sangre , Ciclo Estral/efectos de los fármacos , Femenino , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Hígado/enzimología , Ratones , Ratones Endogámicos BALB C , Tamaño de los Órganos/efectos de los fármacos , Ovario/anatomía & histología , Ovario/efectos de los fármacos , Progesterona/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estradiol/genética , Receptores de Progesterona/genética , Útero/efectos de los fármacos , Útero/metabolismoRESUMEN
Biotin is a water-soluble vitamin that acts as a prosthetic group of carboxylases. Besides its role as carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism. Several studies have reported a relationship between biotin and blood lipids. In the present work we investigated the effect of biotin administration on the concentration of plasma lipids, as well as glucose and insulin in type 2 diabetic and nondiabetic subjects. Eighteen diabetic and 15 nondiabetic subjects aged 30-65 were randomized into two groups and received either 61.4 micromol/day of biotin or placebo for 28 days. Plasma samples obtained at baseline and after treatment were analyzed for total triglyceride, cholesterol, very low density lipoprotein (VLDL), glucose and insulin. We found that the vitamin significantly reduced (P=0.005) plasma triacylglycerol and VLDL concentrations. Biotin produced the following changes (mean of absolute differences between 0 and 28 day treatment+/-S.E.M.): a) triacylglycerol -0.55+/-0.2 in the diabetic group and -0.92+/-0.36 in the nondiabetic group; b) VLDL: -0.11+/-0.04 in the diabetic group and -0.18+/-0.07 in the nondiabetic group. Biotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects. We conclude that pharmacological doses of biotin decrease hypertriglyceridemia. The triglyceride-lowering effect of biotin suggests that biotin could be used in the treatment of hypertriglyceridemia.
Asunto(s)
Biotina/farmacología , Biotina/uso terapéutico , VLDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Hipertrigliceridemia/sangre , Hipertrigliceridemia/tratamiento farmacológico , Triglicéridos/sangre , Adulto , Anciano , Biotina/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
1. The lateral hypothalamus (LH) and the dorsal periaqueductal gray area (dPAG) are two important brain structures involved in central cardiovascular control. 2. In the present study, we searched for possible rostrocaudal somatotopy in the neural connections from the three subdivisions of the LH (anterior-LHa; tuberal-LHt and posterior-LHp) to the different rostrocaudal portions of the dPAG. 3. The bidirectional neuronal tracer biotinylated-dextran-amine (BDA) was microinjected into different rostrocaudal coordinates of the dPAG (AP 3.4-2.7 mm) of male Wistar rats. One week later, animals were sacrificed and brain slices were processed and analyzed to detect neuronal efferent projections from the LH to the dPAG. 4. Neuronal cell body staining was observed along all the rostrocaudal axis of the LH when BDA was microinjected in more rostral dPAG coordinates. When the BDA was microinjected into more caudal dPAG regions, labeled neurons were observed only in the caudal portion of the LH. 5. Efferent projections from the LHa were directed only to the rostral portion of the dPAG. Projections from the rostral and medial portions of the LHt were also directed to the rostral dPAG, whereas both rostral and caudal dPAG received projections from the caudal portion of the LHt. Efferent projections from the anterior portion of the LHp were directed to both rostral and caudal dPAG, whereas projections from the caudal LHp were only directed to the rostral portion of the dPAG.6. The results suggest a somatotopic correlation in LH projections to the dPAG with main connections to the rostral dPAG, which are efferent from the three divisions of the LH. More caudal regions of the dPAG received afferents only from posterior sites in the LH. 7. Moreover, the results point out to extensive and complex neural somatotopic projections from all LH subdivisions to different rostrocaudal portions of the dPAG, reinforcing the idea of significant functional interactions between the brain structures.
Asunto(s)
Mapeo Encefálico , Hipotálamo/anatomía & histología , Sustancia Gris Periacueductal/anatomía & histología , Vías Aferentes/anatomía & histología , Animales , Biotina/administración & dosificación , Biotina/análogos & derivados , Dextranos/administración & dosificación , Vías Eferentes/anatomía & histología , Masculino , Microinyecciones , Modelos Biológicos , Vías Nerviosas/anatomía & histología , Ratas , Ratas WistarRESUMEN
A method for delivering drugs to sites of disease extension in mediastinal nodes is described. Mediastinal node and lymphatic distributions were determined after intracavitary injection of the avidin/biotin-liposome system in normal rats. The effect of the injected dose on lymphatic targeting of liposomes after intraperitoneal injection of (99m)Tc-blue-biotin-liposomes and intrapleural injection of avidin, and vice versa, is presented. Scintigraphic imaging was used to follow the movement of (99m)Tc-blue-biotin-liposomes to determine the pharmacokinetics and organ uptake. Tissue biodistribution studies were performed 22 h after injection of the (99m)Tc-blue-biotin-liposomes. Results indicated that independent of the cavity in which each agent was injected, a dose of 5.0 mg of each agent results in higher mediastinal node targeting (8%-10% ID/Organ) as compared with the injection of a 0.5 mg dose (2%-5% ID/Organ, p < 0.05). Targeting of diaphragm and associated lymphatics was observed when (99m)Tc-blue-biotin-liposomes were injected in peritoneum and avidin in pleural space. In contrast, pleural, and pericardial lymphatic targeting was observed when (99m)Tc-blue-biotin-liposomes were injected in pleural space and avidin in peritoneum. Intracavitary injection of the avidin/biotin-liposome system could potentially be used for the delivery of prophylactic drugs that could reduce tumor metastasis and infection spread to mediastinal nodes.
Asunto(s)
Avidina/farmacocinética , Biotina/farmacocinética , Liposomas/farmacocinética , Animales , Avidina/administración & dosificación , Biotina/administración & dosificación , Diafragma/metabolismo , Inyecciones , Inyecciones Intraperitoneales , Liposomas/administración & dosificación , Ganglios Linfáticos/metabolismo , Vasos Linfáticos/metabolismo , Masculino , Mediastino , Cavidad Pleural , Ratas , Ratas Sprague-Dawley , TecnecioRESUMEN
1. The injection of acetylcholine (ACh) into the medial prefrontal cortex (MPFC) caused marked hypotensive response in either unanesthetized or anesthetized rats. 2. The present experiment was designed to investigate anatomical connections of the ACh injection site in the MPFC with putative autonomic-related brain nuclei, as well as their possible involvement in the mediation of the hypotensive response to ACh. 3. For the above purpose, the bidirectional neuronal tracer biotinylated dextran amine (BDA) was injected into Cg1 and Cg3 areas, within the MPFC of male Wistar rats. Five days later the animals were sacrificed and brain slices were processed and analyzed to determine neuronal projections efferent from as well afferent to the MPFC. 4. Neuronal staining was more prominent in regions ipsilateral to the BDA injection site. Prominent efferent projections of the MPFC were observed in the contralateral MPFC: ipsi- and contralateral amygdala and hypothalamus; ipsilateral septal area, diagonal band, and zona incerta. 5. Similar but not equal patterns of neuronal labeling were observed when BDA injections were performed within the two adjacent MPFC areas. BDA injections centered in the ACh injection site in the Cg3 area caused strong labeling in the septal area and diagonal band as well as an overall hypothalamic labeling. Within the hypothalamus an intense cortical projection was observed in the lateral hypothalamus (LH). BDA injections into the Cg1 area caused a more evident labeling of the amygdaloid complex. 6. Neuronal cell bodies were evident throughout the MPFC as well as in the sensory-motor cortex when BDA was injected into the LH, thus indicating a massive ipsilateral cortical projection from the Cg3 to the LH. 7. Bilateral NMDA-induced lesions within the LH caused a significant attenuation of the depressor responses to ACh injection in the MPFC, whereas unilateral lesions were marginally effective. These results indicate the involvement of the LH in the mediation of the hypotensive response to ACh injection into the MPFC as well as the bilateral distribution of the hypotensive pathway.