RESUMEN
Soy isoflavones (IFs) have shown a bone-sparing effect through epidemiological studies in the Asian population. However, there is no evidence as to whether such protection would result from a lifelong exposure. We investigated the impact of an early exposure to IFs on bone status. Sixty female Wistar rats were fed either a standard diet (n=30) or the same food enriched with IFs (0.87 mg/g of diet) (n=30). After 1 month, they were allowed to mate, and were kept on the same regimen during the whole gestation and lactation periods. At weaning, female pups were each assigned to one of four nutritional groups; within each experimental group, animals were split into two groups, fed either the standard or the IF-rich diet. At 2, 3, 6, 12, 18, and 24 months after birth, 10 animals in each group were sacrificed. Femurs were collected for mechanical testing and bone mineral density (BMD) measurement. The rats perinatally or lifelong exposed to the IF-rich diet exhibited higher body weight and fat mass at 24 months of age. Peak bone mass was achieved between 6 and 12 months and did not differ between groups. In animals perinatally exposed to IF, BMD continued to increase. Thus, at 24 months, femoral total BMD (P<0.05), metaphyseal BMD (P<0.01), and failure load (P<0.05) were higher in the offspring born from mothers provided IF during pregnancy. Postnatal exposure alone did not improve bone parameters. This experiment provides evidence that perinatal exposure to phytoestrogens leads to a higher BMD later in life. It is suggested that these changes may have occurred as a consequence of programming effects, as has been shown for the endocrine and immune systems.
Asunto(s)
Envejecimiento/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Glycine max/química , Isoflavonas/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Biomarcadores/orina , Peso Corporal/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Femenino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Útero/efectos de los fármacosRESUMEN
INTRODUCTION: Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor. METHODS: A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 microg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 mug/g body weight/d, simultaneously with short-chain FOS (Actilight, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX. RESULTS: Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant. CONCLUSION: In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.
Asunto(s)
Densidad Ósea/fisiología , Glycine max/química , Isoflavonas/farmacología , Osteoporosis/prevención & control , Fitoestrógenos/farmacología , Animales , Biomarcadores/análisis , Peso Corporal/fisiología , Resorción Ósea/fisiopatología , Modelos Animales de Enfermedad , Equol , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Genisteína/sangre , Genisteína/farmacología , Isoflavonas/sangre , Tamaño de los Órganos , Osteocalcina/sangre , Osteoporosis/metabolismo , Ovariectomía , Fitoestrógenos/sangre , Ratas , Ratas Wistar , Útero/patologíaRESUMEN
Aging and sex hormones related changes lead to inflammatory and oxidant conditions, which are involved in the pathogenesis of osteoporosis. Recent studies have suggested that polyphenols may exert a protective effect in such conditions. We assessed the effect of phloridzin (Phlo), a flavonoid exclusively found in apple, on bone metabolism in ovariectomized (OVX) or sham-operated (SH) rats with and without inflammation. Six-month-old Wistar rats were allocated to two equal groups that received either a control diet or a diet supplemented with 0.25% Phlo for 80 days. Three weeks before necropsy, inflammation was induced by subcutaneous injection of talc in 10 animals of each group. At necropsy, ovariectomy decreased both total (T-BMD) and metaphyseal (M-BMD) femoral bone mineral density (P < 0.01). Inflammation conditions, checked by an increase in the spleen weight and alpha1-acid glycoprotein concentration in OVX rats, exacerbated the decrease in T-BMD (g/cm2) (as well as M-BMD) observed in castrated animals (P < 0.05). Daily Phlo intake prevented ovariectomy-induced bone loss in conditions of inflammation as shown by T-BMD and M-BMD (P < 0.05). At the diaphyseal site, BMD was improved by Phlo in OVX rats with or without inflammation (P < 0.05). These results could be explained by changes in bone remodeling as the increased urinary deoxypyridinoline excretion in OVX and OVXinf animals was prevented by the polyphenol-rich diet (P < 0.001), while plasma osteocalcin concentration was similar in all experimental groups. In conclusion, Phlo consumption may provide protection against ovariectomy-induced osteopenia under inflammation conditions by improving inflammation markers and bone resorption.
Asunto(s)
Enfermedades Óseas Metabólicas/prevención & control , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Inflamación/tratamiento farmacológico , Malus/química , Florizina/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/fisiopatología , Resorción Ósea/fisiopatología , Modelos Animales de Enfermedad , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Fémur/fisiopatología , Inflamación/complicaciones , Inflamación/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Osteocalcina/sangre , Ovariectomía , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Estrés Mecánico , Soporte de PesoRESUMEN
Because the biggest culprit in pathogenesis of osteoporosis is oestrogen deficiency, hormone replacement therapy remained the mainstay for prevention. However most of postmenopausal women are more inclined to use natural alternative. We thus investigated the ability of Abelmoschus manihot, a herbal medicine to prevent bone loss in ovariectomised rats. Female Wistar rats were sham operated (SH: 8) or ovariectomised (OVX: 24). On day 0, OVX rats were randomly assigned to groups as follows: eight received 10% Abelmoschus manihot leaves in their diet, eight were given 15% Abelmoschus manihot leaves and eight were untreated (OVX). Compounds were mixed with a soy protein-free diet and given orally for 3 months. At necropsy, bone mineral density (BMD) in the femur and in its metaphyseal zone was lower in OVX than SH (p<0.05). This osteopenia was prevented by consumption of the highest dose of Abelmoschus manihot leaves. Bone mineral content (BMC) in the total femur and its metaphyseal and diaphyseal subregions was improved, as well (p<0.05). This could be explained by a trend towards decreased bone resorption. The lowest dose did not elicit any significant effect. In conclusion, Abelmoschus manihot consumption, at the dose of 15% in the diet, provided bone-sparing effects by improving both BMD and BMC.
Asunto(s)
Abelmoschus/química , Osteoporosis Posmenopáusica/prevención & control , Ovariectomía , Fitoterapia , Absorciometría de Fotón , Animales , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Huesos/metabolismo , Femenino , Humanos , Tamaño de los Órganos/efectos de los fármacos , Osteocalcina/sangre , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Útero/efectos de los fármacosRESUMEN
Isoflavones (IF) have been increasingly implicated for use in the prevention of osteoporosis. As their bioavailability could be improved by modulating intestinal microflora, the present study was undertaken to investigate whether IF and fructooligosaccharides (FOS), which are known to modify large-bowel flora and metabolism, may exhibit a cooperative bone-sparing effect. This work was carried out on 3-month-old Wistar rats assigned to 12 groups: 2 SH (sham-operated) and 10 OVX (ovariectomized). Animals received a diet for 90 days containing total IF (Prevastei HC, Central Soya) at 0 (OVX and SH), 10 (IF10), 20 (IF20), 40 (IF40), or 80 (IF80) microg/g body weight per day. FOS (Actilight, Beghin-Meiji) were orally given to half of the groups, (OVX FOS), (IF10 FOS), (IF20 FOS), (IF40 FOS), (IF80 FOS), and (SH FOS). Isoflavones exhibited a bone-sparing effect as soon as consumption reached 20 microg/g/day, whereas only the highest dose induced a weak uterotrophic activity. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared with that of OVX rats), as was the metaphyseal compartment. Bone strength was improved as well. As far as the FOS diet is concerned, addition of prebiotics significantly raised the efficiency of the IF protective effect on both femoral BMD and mechanical properties. The trend toward higher BMD levels with the lowest IF dose (IF10) even reached a significant level when FOS were added. This effect could be explained by a reduced bone resorption. In conclusion, daily IF consumption prevented castration-induced osteopenia by decreasing bone resorption when given at 20, 40, or 80 microg (total isoflavones)/g/day. Simultaneous FOS consumption improved IF protective effect on the skeleton, with the lowest IF dose becoming efficient. Enhancement of IF bioavailability, following FOS fermentation, is probably involved.
Asunto(s)
Huesos/efectos de los fármacos , Isoflavonas/farmacología , Oligosacáridos/farmacología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Animales , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Desarrollo Óseo/efectos de los fármacos , Desarrollo Óseo/fisiología , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Resorción Ósea/fisiopatología , Huesos/metabolismo , Huesos/fisiopatología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Fémur/efectos de los fármacos , Fémur/crecimiento & desarrollo , Fémur/metabolismo , Alimentos Formulados , Humanos , Isoflavonas/uso terapéutico , Oligosacáridos/uso terapéutico , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/fisiopatología , Ovariectomía , Ratas , Ratas Wistar , Alimentos de Soja , Resultado del TratamientoRESUMEN
The pharmacological properties of Caesalpinia bonduc Roxb. (Caesalpiniaceae) are not well known, but it is used traditionally to treat snake bite (Bellomaria and Kacou, 1995; Schaffner, 1997). In the present study, the mechanism through which Caesalpinia bonduc extract (Cebo) affects gallamine-induced relaxation in rat tibial muscle contractility were studied via measurement of isometric-tension-anesthetized, 10-12-week-old, male rats. Isometric twitch contractions of the indirectly-stimulated anterior tibia muscle of the right hindleg were recorded in situ. Cebo administered intravenously (i.v.) increased twitch contractions in a dose-dependent manner. The ED50 value is 2.75 x 10(-4) g/kg body wt. Similar results were obtained using the anticholinesterase neostigmine. In contrast, gallamine (a non-depolarizing muscle relaxant) or the venom of the puff adder Bitis arietans reduced the force of contraction. Treatment with Cebo or neostigmine, however, reversed the relaxation induced by either gallamine or puff adder venom. In conclusion, Cebo stimulates the muscle contractile activity, an effect which may be due to an activation of the cholinergic mechanism.
Asunto(s)
Caesalpinia , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Animales , Relación Dosis-Respuesta a Droga , Venenos Elapídicos/farmacología , Estimulación Eléctrica , Inyecciones Intravenosas , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas , Ratas Wistar , ViperidaeRESUMEN
We investigated the ability of genistein and daidzein, two soybean isoflavones, compared with that of 17 alpha-ethinylestradiol, to prevent bone loss in ovariectomized rats, a model for postmenopausal osteoporosis. Female Wistar rats (n = 65; 12 mo old) were either sham-operated (SH; n = 13) or ovariectomized (OVX; n = 52). On d 0, OVX rats were randomly assigned to groups as follows: 13 received genistein [G; 10 mcg/(g body weight. d)], 13 were treated with daidzein [D; 10 mcg/(g body weight. d)], 13 received 17 alpha-ethinylestradiol [E(2); 30 mcg/kg body weight. d)] and 13 were untreated (OVX). Compounds were mixed with a soy protein-free powdered semipurified diet and given orally for 3 mo. On d 90, the bone mineral density (BMD) in lumbar vertebrae, femur and its metaphyseal and diaphyseal zones (rich in cancellous and cortical bone, respectively) was lower in OVX than in SH (P < 0.01). In D or E(2), the four BMD were not different from SH, whereas in G, only the diaphyseal BMD was not different from SH. Image analysis performed in the distal femur metaphysis revealed that the cancellous bone area was lower in OVX than in SH (P < 0.01). Only the area in D was not different from that in SH. Finally, the bone turnover, which was higher in OVX than in SH (P < 0.005 and P < 0.05 for plasma osteocalcin concentration and urinary deoxypyridinoline excretion, respectively), was not different in G, D or E(2) compared with SH. Therefore, consumption of 17 alpha-ethinylestradiol or daidzein was more efficient than genistein in preventing ovariectomy-induced bone loss in rats.
Asunto(s)
Estrógenos no Esteroides/farmacología , Genisteína/farmacología , Isoflavonas/farmacología , Osteoporosis Posmenopáusica/prevención & control , Ovariectomía/efectos adversos , Animales , Peso Corporal/efectos de los fármacos , Densidad Ósea , Equidae , Estrógenos no Esteroides/sangre , Femenino , Cabras , Humanos , Osteocalcina/sangre , Osteoporosis Posmenopáusica/etiología , Fitoestrógenos , Preparaciones de Plantas , Radioinmunoensayo , Ratas , Ratas WistarRESUMEN
Plasma renin activity, plasma aldosterone and arginine-vasopressin concentrations were determined in five diarrhoeic and five healthy newborn calves. In animals suffering from diarrhoea these three parameters were 10-15 times higher than those observed in controls. These results suggest that the hormonal systems that control fluid and electrolyte homeostasis are highly stimulated by dehydration and salt depletion induced by faecal losses of water and sodium in calves affected with diarrhoea.
Asunto(s)
Arginina Vasopresina/sangre , Enfermedades de los Bovinos/metabolismo , Diarrea/veterinaria , Sistema Renina-Angiotensina/fisiología , Aldosterona/sangre , Animales , Animales Recién Nacidos , Bovinos , Diarrea/metabolismo , Renina/sangreRESUMEN
The effects of normotensive and hypotensive hypovolaemia (haemorrhage) as well as isovolaemic hypotension (nitroprusside administration) on diastolic, systolic and mean arterial blood pressure, heart rate and plasma concentrations of arginine vasopressin were studied in two sets of experiments on 8-10 days old conscious newborn calves bearing an indwelling aortic catheter for continuous recording of arterial blood pressure. Removal of 20% of the estimated blood volume resulted in an average maximum decrease of systolic, diastolic and mean arterial blood pressure from 132 +/- 2 to 118 +/- 8 mm Hg (P less than 0.05), from 72 +/- 2 to 67 +/- 2 mmHg (P less than 0.05) and from 92 +/- 3 to 82 +/- 6 mmHg (P less than 0.05) respectively. In the same time heart rate increased from 124 +/- 3 to 143 +/- 5 beats.min-1. Plasma concentrations of arginine vasopressin increased before blood loss had induced any change in arterial blood pressure (from 5.7 +/- 0.7 pg/ml-1 at time 0 to 25.2 +/- 3 pg/ml-1 at time 20 min; P less than 0.01). The significant fall in blood pressure was accompanied by a further prompt increase in plasma concentration of arginine vasopressin which reached maximum values (90.1 +/- 9.7 pg/ml-1) at completion of haemorrhage. The conscious newborn calf responded to i.v. nitroprusside infusion (10 micrograms/kg-1/min-1 for 10 min) with a prompt fall in diastolic (-71%, P less than 0.01), systolic (-70%, P less than 0.01) and mean (-56%, P less than 0.01) arterial blood pressure within 3 min of the infusion. Time course changes in heart rate were opposite to those in arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Animales Recién Nacidos/fisiología , Arginina Vasopresina/sangre , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Hemorragia/fisiopatología , Nitroprusiato/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Bovinos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hematócrito , Infusiones Intravenosas , Masculino , Concentración Osmolar , Potasio/sangre , Valores de Referencia , Sodio/sangreRESUMEN
Systemic plasma concentrations of arginine vasopressin (AVP) were studied in three groups of 10-15 day-old conscious newborn calves. Animals in the first group (control group) and in the second group (systemic-hypertonic-injected group) received respectively isotonic and hypertonic (8 mmol NaCl/kg body weight) saline injection into the right jugular vein. Animals in the third group were fitted with chronic mesenteric and hepatic-portal catheters and received a 1 h-hypertonic saline infusion (2 mmol NaCl/kg body weight) into the main mesenteric vein. In animals in the second group there were parallel increases in systemic plasma concentration of Na+ (from 148.0 +/- 2.6 to 177 +/- 8 mmol/l; P less than 0.01), osmolality (from 289 +/- 2 to 319 +/- 4 mOsmol/kg H2O; P less than 0.01) and systemic plasma concentrations of AVP (from 4.2 +/- 0.4 to 11.1 +/- 0.6 pmol/l; P less than 0.01) 10 min after the injection. There were no significant changes in control animals. Hypertonic saline infusion into the main mesenteric vein in the third group induced an increase in concentration of Na+ (from 147.3 +/- 2.0 to 165.0 +/- 5.0 mmol/l; P less than 0.01) and osmolality (from 288 +/- 5 to 315 +/- 10 mOsmol/kg H2O; P less than 0.01) in hepatic-portal vein plasma but did not alter systemic plasma osmolality or concentrations of Na+ and AVP. This study demonstrates that the relationship between plasma concentrations of AVP and systemic osmolality is operative in the newborn calf but does not support the hypothesis that hepatic portal osmo-receptors sensitive to hyperosmolality influence AVP release.