RESUMEN
During the spawning process in starfish, oocytes are arrested at metaphase of meiosis I (MI) within the ovary, and reinitiate meiosis only after they have been released into the seawater. However, this arrest does not occur if the ovary is removed from the animal. As the pH of the coelomic fluid is buffered by CO2/H(+)/HCO3(-), we investigated the involvement of gas concentrations in MI arrest. In vivo, the CO2 level in the coelomic fluid was high (â¼1.5% vs. 0.04% in air) and the O2 level was low (0.1-1.0% vs. â¼20% in air). When these gas conditions were reproduced in isolated coelomic fluid or seawater, ovarian oocytes arrested at MI, just as in vivo. Isolated oocytes from the ovary required the similar high CO2 and low O2 level to remain arrested in MI and had an intracellular pH of â¼6.9. Intracellular pH increased to â¼7.3 when oocytes were transferred to seawater equilibrated with air, a condition that mimics that of spawning. We used ammonium acetate to clamp intracellular pH at different levels and found that MI arrest occurred when intracellular pH was â¼6.9. Our results support the idea that high CO2 and low O2 in the ovarian environment lead to low intracellular pH and MI arrest, while spawning into the seawater with low CO2 and high O2 results in high intracellular pH and release from MI arrest. The biological significance of MI arrest is that oocytes are spawned into seawater at the optimal physiological state of MI when the least polyspermy occurs.
Asunto(s)
Dióxido de Carbono/farmacología , Líquido Extracelular/química , Meiosis/efectos de los fármacos , Oocitos/efectos de los fármacos , Oxígeno/farmacología , Estrellas de Mar , Animales , Dióxido de Carbono/química , Concentración de Iones de Hidrógeno , Oocitos/citología , Oocitos/fisiología , Oxígeno/químicaRESUMEN
The effects of keishibukuryogan on the early stage of progressive renal failure were examined in rats subjected to 5/6 nephrectomy. Keishibukuryogan, one of the traditional herbal formulations, was given orally at a dose of 1% (w/w) and 3% (w/w) in chow. Administration of keishibukuryogan was started at 1 week after 5/6 nephrectomy and was continued for 4 weeks. At the end of the experiment, Azan staining did not reveal any severe histological changes in the kidneys of the nephrectomized rats. On the other hand, significant increases in mRNA expressions of transforming growth factor-ß(1) and fibronectin related to tissue fibrosis, as examined by Reverse Transcriptase-Polymerase Chain Reaction, were observed in nephrectomized rats, and they were significantly suppressed by 3% keishibukuryogan treatment. Against gene expressions related to macrophage infiltration, 3% keishibukuryogan treatment significantly suppressed osteopontin mRNA levels, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 mRNA levels showed a tendency to decrease, but without statistical significance. It was also observed that 3% keishibukuryogan attenuated serum urea nitrogen and urinary protein excretion levels. From these results, it was suggested that keishibukuryogan exerts beneficial effects that result in slowing the progression of chronic renal failure.
RESUMEN
Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. In this study, we examined the effects of keishibukuryogan on glucose and lipids metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Forty-five-week-old male OLETF rats were divided into three groups: diabetic control rats given a standard chow; diabetic rats given keishibukuryogan (3%, w/w in chow); diabetic rats given pioglitazone (0.01%, w/w in chow). Oral administration of keishibukuryogan produced significant improvement against impaired glucose tolerance. On the other hand, fasting serum glucose and insulin levels, and the homeostasis index of insulin resistance did not change by keishibukuryogan treatment. Against lipid parameters, keishibukuryogan significantly lowered serum total cholesterol and triglyceride levels, and the hepatic total cholesterol level. Keishibukuryogan treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. Additionally, keishibukuryogan showed significant effects on epididymal adipose tissue by decreasing the size of fat cells and on skeletal muscle by reducing TNF-alpha protein content. From these results, it was suggested that keishibukuryogan exerts beneficial effects on the features associated with type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Intolerancia a la Glucosa/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Fitoterapia , Adiponectina/sangre , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Homeostasis/efectos de los fármacos , Hipoglucemiantes/farmacología , Insulina/sangre , Leptina/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Pioglitazona , Ratas , Ratas Endogámicas OLETF , Tiazolidinedionas/farmacología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
It is known that rheumatoid arthritis (RA) accelerates atherosclerosis. Further, the soluble form of vascular adhesion molecule-1 (VCAM-1) is known as a predictive marker of atherosclerosis in RA patients. We reported that keishibukuryogan, one of the Kampo formulas, improved articular symptoms and decreased soluble VCAM-1 in patients with RA. In adjuvant-induced arthritis (AIA) rats, an animal model of RA, it is known that endothelial function is injured by inflammation. So, we investigated the effect of keishibukuryogan on endothelial function in AIA rats. Lewis rats were divided into control, AIA control, and AIA with keishibukuryogan groups. The AIA with keishibukuryogan group was fed 3% keishibukuryogan contained in normal chow. On day 25 after injection of Mycobacterium butyricum, endothelium-dependent relaxation by acetylcholine in the AIA control group was suppressed, but it was improved in the AIA with keishibukuryogan group. The contractions by xanthine/xanthine oxidase in both AIA rats increased, but that in keishibukuryogan decreased compared to the AIA control group. Plasma levels of lipid peroxide increased in the AIA control group, but keishibukuryogan decreased these levels. Plasma levels of nitric oxide (NO) increased in both AIA groups. The expressions of endothelial NO synthase, inducible NO synthase and VCAM-1 of thoracic aorta were investigated by western blotting. These expressions increased in the AIA control group, but were restricted in the AIA with keishibukuryogan group. We considered that keishibukuryogan protected the endothelial function of AIA rats mainly by its anti-oxidative effect.
Asunto(s)
Antioxidantes/farmacología , Artritis Experimental/metabolismo , Medicamentos Herbarios Chinos/farmacología , Endotelio Vascular/efectos de los fármacos , Medicina Kampo , Acetilcolina/farmacología , Animales , Aorta Torácica/enzimología , Aorta Torácica/metabolismo , Artritis Experimental/inducido químicamente , Artritis Experimental/fisiopatología , Adyuvante de Freund , Peroxidación de Lípido/efectos de los fármacos , Masculino , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Perfusión , Distribución Aleatoria , Ratas , Ratas Endogámicas Lew , Molécula 1 de Adhesión Celular Vascular/metabolismo , Vasodilatadores/farmacología , Xantina/farmacología , Xantina Oxidasa/farmacologíaRESUMEN
Glucose and lipid metabolic parameters play crucial roles in metabolic syndrome and its major feature of insulin resistance. This study was designed to investigate whether dietary astaxanthin oil (ASX-O) has potential effects on metabolic syndrome features in an SHR/NDmcr-cp (cp/cp) rat model. Oral administration of ASX (50 mg/kg/day) for 22 weeks induced a significant reduction in arterial blood pressure in SHRcp. It also significantly reduced the fasting blood glucose level, homeostasis index of insulin resistance (HOMA-IR), and improved insulin sensitivity. The results also showed an improved adiponectin level, a significant increase in high-density lipoprotein cholesterol, a significant decrease in plasma levels of triglycerides, and non-esterified fatty acids. Additionally, ASX showed significant effects on the white adipose tissue by decreasing the size of the fat cells. These results suggest that ASX ameliorates insulin resistance by mechanisms involving the increase of glucose uptake, and by modulating the level of circulating lipid metabolites and adiponectin.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/prevención & control , Resistencia a la Insulina , Síndrome Metabólico/prevención & control , Adiponectina/sangre , Tejido Adiposo/citología , Tejido Adiposo/efectos de los fármacos , Administración Oral , Animales , Recuento de Células Sanguíneas , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Hipertensión/sangre , Hipertensión/metabolismo , Hipertensión/fisiopatología , Insulina/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/metabolismo , Síndrome Metabólico/fisiopatología , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Xantófilas/administración & dosificación , Xantófilas/farmacología , Xantófilas/uso terapéuticoRESUMEN
Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. It consists of the following five crude drugs: Cinnamomi Cortex, Poria, Moutan Cortex, Persicae Semen and Paeoniae Radix. In this study, the effects of keishibukuryogan against renal damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of keishibukuryogan significantly attenuated urinary protein excretion and serum creatinine levels. It did not affect body weight loss and blood glucose levels, but it suppressed renal and hepatic weights of WBN/Kob rats. Keishibukuryogan also reduced fibronectin and transforming growth factor beta(1) (TGF-beta(1)) protein expression in the renal cortex. Furthermore, lipid peroxidation levels in both kidney and liver were significantly lower than those of untreated control WBN/Kob rats. Urinary excretion of 8-hydroxy-deoxyguanosine was suppressed by keishibukuryogan treatment. These results suggest that keishibukuryogan reduces oxidative stress by hyperglycemia, and that it protects renal function and suppresses fibronectin deposition induced by TGF-beta(1) production in WBN/Kob rats.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Riñón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Glucemia/efectos de los fármacos , Creatinina/sangre , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Fibronectinas/efectos de los fármacos , Hiperglucemia/fisiopatología , Riñón/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Medicina Tradicional , Tamaño de los Órganos/efectos de los fármacos , Fitoterapia , Preparaciones de Plantas/farmacología , Preparaciones de Plantas/uso terapéutico , Sustancias Protectoras , Proteinuria/tratamiento farmacológico , Ratas , Ratas Wistar , Factor de Crecimiento Transformador beta1/efectos de los fármacos , Pérdida de Peso/efectos de los fármacosRESUMEN
The vasorelaxant effect of cinnamaldehyde, one of the major oil components in Cinnamomi Cortex, was studied using isolated rat aorta. Cinnamaldehyde at final concentrations of 1 microM to 1 mM showed dose-dependent relaxation of the rat aorta contracted by treatment with prostaglandin F2alpha, norepinephrine or KCl. In addition, cinnamaldehyde relaxed prostaglandin F2alpha-precontracted aortic rings with endothelium and without endothelium, with the latter being significantly less sensitive than the former. Relaxation induced by cinnamaldehyde with endothelium was significantly inhibited by NG-nitro-L-arginine methyl ester (L-NAME), while nonselective cyclooxygenase inhibitor (indomethacin), beta-adrenergic receptor blocker (propranolol), an inhibitor of phosphodiesterase (theophylline), a delayed rectifier K+ channel blocker (tetraethyl ammonium chloride), or an ATP-sensitive K+ channel blocker (glibenclamide) did not reduce the relaxation induced by cinnamaldehyde with endothelium treated by L-NAME. Conversely, aorta pretreatment with L-NAME and theophylline increased the relaxation by cinnamaldehyde significantly compared to aorta pretreatment with only L-NAME. Furthermore, cinnamaldehyde significantly inhibited Ca2+-induced contraction. These results suggested that the vasorelaxant effects of cinnamaldehyde were derived from both endothelium-dependent and -independent effects. Endothelium-dependent relaxation is affected by nitric oxide, and one of the mechanisms of endothelium-independent relaxation is thought to be influenced by the blocking of Ca2+ channels.
Asunto(s)
Acroleína/análogos & derivados , Aorta/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Acroleína/farmacología , Animales , Aorta/fisiología , Endotelio Vascular/fisiología , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacología , Ratas , Ratas WistarRESUMEN
An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS(28)). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS(28) decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients.
RESUMEN
Wen-pi-tang is a Chinese prescription used traditionally as a medicine to treat moderate renal failure. In this study, we used rats subjected to subtotal nephrectomy and streptozotocin injection to examine the effects of wen-pi-tang on diabetic nephropathy. Wen-pi-tang was administered at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. Diabetic nephropathy is one of the most serious chronic complications of diabetes mellitus, and renal dysfunction is reflected by proteinuria, decreased creatinine clearance (Ccr) and increased serum urea nitrogen and creatinine (Cr) levels. Wen-pi-tang treatment for 15 weeks resulted in significant reductions of blood glucose and serum urea nitrogen levels, while proteinuria, Ccr and serum Cr levels did not change significantly. Wen-pi-tang also lowered serum triglyceride and thiobarbituric acid-reactive substance levels in a dose-dependent manner. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were normalized by the administration of wen-pi-tang through decreased formation of advanced glycation end-products in the kidney. Wen-pi-tang protected against the development of renal lesions, glomerular sclerosis and mesangial matrix expansion, assessed by histopathological evaluation and scoring. This study suggests that wen-pi-tang treatment could be beneficial in reducing the risk of developing diabetic nephropathy.
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Animales , Glucemia/análisis , Nitrógeno de la Urea Sanguínea , Relación Dosis-Respuesta a Droga , Productos Finales de Glicación Avanzada/análisis , Masculino , Ratas , Ratas Wistar , Estreptozocina , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
The effects of gamma-aminobutyric acid (GABA) in rats with experimental diabetes mellitus were examined. Diabetes mellitus was induced in adult male Wistar rats by streptozotocin (STZ) injection. Oral administration of GABA (100 or 200 mg/kg body weight/d) for 10 d to the diabetic rats resulted in a significant decrease in their serum glucose level. GABA also reduced the level of glycosylated protein in serum, indicating an improvement of hyperglycemic conditions. Rats with STZ-induced diabetes showed arrested body weight gain and an increase in both liver and kidney weight, whereas oral administration of GABA attenuated the organ hypertrophy induced by hyperglycemia. In addition, the degree of serum thiobarbituric acid (TBA)-reactive substance level was significantly lower in the rats treated with 100 mg GABA, and the degree of TBA-reactive substance in the liver and kidney was reduced by GABA in a dose-dependent manner. These results suggest that GABA treatment protects against the development of diabetic complications resulting from impaired glucose metabolism and enhanced oxidative stress.
Asunto(s)
Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Ácido gamma-Aminobutírico/administración & dosificación , Animales , Glucemia/análisis , Diabetes Mellitus Experimental/fisiopatología , Hemoglobina Glucada/análisis , Riñón/química , Riñón/patología , Hígado/química , Hígado/patología , Masculino , Tamaño de los Órganos , Estrés Oxidativo , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Aumento de PesoRESUMEN
The effects of proanthocyanidin-rich extract in rats subjected to renal ischemia-reperfusion were examined. Proanthocyanidin-rich extract, which is prepared from grape seeds (Vitis vinifera L.), was given orally at doses of 5 and 10 mg/kg body weight/d for 20 consecutive days prior to ischemia-reperfusion. Administration of proanthocyanidin-rich extract attenuated renal dysfunction, as indicated by serum urea nitrogen and creatinine levels. Additionally, in the ischemic-reperfused kidneys, increased levels of thiobarbituric acid (TBA)-reactive substance and alterations of antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase (GSH-Px) were observed. Proanthocyanidin-rich extract-treated groups showed significantly reduced renal TBA-reactive substance levels and enhanced catalase and GSH-Px activities. These results suggest that proanthocyanidin-rich extract has protective effects against ischemia-reperfusion-induced renal damage associated with oxidative stress.
Asunto(s)
Riñón/irrigación sanguínea , Extractos Vegetales/administración & dosificación , Proantocianidinas/administración & dosificación , Daño por Reperfusión/prevención & control , Semillas/química , Vitis/química , Animales , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
Wen-Pi-Tang, an Oriental medical prescription composed of Rhei Rhizoma, Ginseng Radix, Aconiti Tuber, Zingiberis Rhizoma and Glycyrrhizae Radix, is used clinically as a medicine to treat renal failure. This study was conducted to examine the inhibitory activity of the five crude drug components of Wen-Pi-Tang and several pure compounds isolated from Rhei Rhizoma and Glycyrrhizae Radix against the protein glycation reaction. Rhei Rhizoma exerted the most potent activity, Zingiberis Rhizoma and Glycyrrhizae Radix showed relatively moderate activity, whereas Aconiti Tuber and Ginseng Radix showed weak activity. On the other hand, of 20 compounds obtained from Rhei Rhizoma and Glycyrrhizae Radix, tannins, especially rhatannin, RG-tannin and procyanidin B-2 3,3'-di-O-gallate, showed significantly strong activities that were more effective than the positive control, aminoguanidine. Some flavones such as licochalcone A and licochalcone B, and anthraquinones such as emodin and aloe-emodin, also showed inhibitory activity. These findings may help to explain, at least in part, certain pharmacological activities of Wen-Pi-Tang, whose clinical efficacy against renal failure is already recognized.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Solución Hipertónica de Glucosa , Productos Finales de Glicación Avanzada/análisis , Glycyrrhiza , Rheum , Albúmina Sérica Bovina/análisis , Depresión Química , Relación Dosis-Respuesta a Droga , Glicosilación/efectos de los fármacosRESUMEN
Diabetes mellitus is now the most common cause of end-stage renal failure. In this study, the effects of Hachimi-jio-gan on diabetic kidney damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of Hachimi-jio-gan to WBN/Kob rats for 25 weeks significantly suppressed urinary protein excretion. It did not affect body weight loss or blood glucose levels, whereas it reversed the increase in kidney weight of WBN/Kob rats. Hachimi-jio-gan also reduced fibronectin and transforming growth factor beta1 (TGF-beta1) protein expression in the renal cortex. Furthermore, renal lipid peroxidation levels of WBN/Kob rats given Hachimi-jio-gan were significantly lower than those of untreated controls. Renal superoxide dismutase activity was elevated by Hachimi-jio-gan treatment in a dose-dependent manner. These results suggested that Hachimi-jio-gan could prevent diabetic kidney damage by reducing renal oxidative injury and expression of fibronectin and TGF-beta1 proteins, which are all involved in the pathophysiology of diabetic nephropathy.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Administración Oral , Animales , Glucemia , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Diabetes Mellitus Experimental/genética , Nefropatías Diabéticas/etiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Fibronectinas/efectos de los fármacos , Fibronectinas/genética , Fibronectinas/metabolismo , Corteza Renal/efectos de los fármacos , Corteza Renal/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Proteinuria/tratamiento farmacológico , Ratas , Ratas Endogámicas , Ratas Wistar , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de Tiempo , Factor de Crecimiento Transformador beta/efectos de los fármacos , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Orina/químicaRESUMEN
In this study we examined the effect of green tea polyphenols (GTP) and partially hydrolysed guar gum (PHGG) as dietary fibre on diabetic nephropathy, using rats that had been subjected to subtotal nephrectomy and injection of streptozotocin. The subtotally nephrectomized rats were subjected to resection of three-quarters of the kidney. Rats with diabetic nephropathy were divided into four groups: untreated controls, and animals that received GTP (100 mg kg-1 body weight day-1), PHGG (100 mg kg-1 body weight day-1) and GTP plus PHGG (50 mg kg-1 body weight day-1 plus 50 mg kg-1 body weight day-1). After 50 days of administration, attenuation of urinary protein excretion and the morphological changes peculiar to diabetic nephropathy were observed in all three treated groups. Furthermore, the group treated with GTP plus PHGG showed an improvement of kidney weight and serum levels of urea nitrogen, creatinine and creatinine clearance. Hyperglycaemia, as assessed in terms of blood glucose and glycosylated protein levels, was also improved by administration of GTP plus PHGG. On the other hand, GTP administration increased the activity of superoxide dismutase in the kidney to a significant extent. A significant reduction in the total cholesterol concentration was also observed in the PHGG-treated group. These results suggest that GTP and PHGG could be beneficial as additional therapy in the management of diabetic nephropathy.
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Flavonoides/uso terapéutico , Galactanos/administración & dosificación , Riñón/efectos de los fármacos , Mananos/administración & dosificación , Fenoles/uso terapéutico , Té , Animales , Glucemia/efectos de los fármacos , Colesterol/sangre , Nefropatías Diabéticas/metabolismo , Fibras de la Dieta/administración & dosificación , Riñón/patología , Riñón/fisiopatología , Pruebas de Función Renal , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Gomas de Plantas , Polifenoles , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
We investigated the changes (increase or decrease in peak intensity) in the expression of plasma proteins in spontaneously diabetic WBN/Kob rats that were with complicated diabetic nephropathy, to determine multiple biomarkers in the plasma of diabetic rats. The present study using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) demonstrated that six peaks at mass/charge ratios (m/z) of 4678, 4732, 4808, 9058, 9323, and 9465, among approximately 80 peaks per spectrum in the 2000-10000 Da mass range, had increased peak intensities with the development or progression of diabetic nephropathy in plasma of spontaneously diabetic WBN/Kob rats as compared with those of normal Wistar rats. Administration of the Kampo medicine Hachimi-jio-gan was effective at reducing the expression of diabetic nephropathy but not at reducing blood glucose levels. It also improved the increased levels of these plasma proteins. Other biomarker peaks at m/z 5067, 5279, 7598, and 7917 were not affected by Hachimi-jio-gan administration. Further study will be needed to identify these positive biomarkers and to evaluate the relationship between the efficacy and expression patterns of the plasma proteins in greater detail. The expression patterns of proteins and molecular-related ions revealed that several proteins in plasma may be involved in the development and/or progression of diabetic nephropathy in WBN/Kob rats and the efficacy of Hachimi-jio-gan. This study using ProteinChip technology may provide a useful basis in the search for multiple biomarkers in plasma for the diagnosis of disease and therapeutic evaluation of Kampo medicines.
Asunto(s)
Proteínas Sanguíneas/biosíntesis , Diabetes Mellitus/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Medicina Kampo , Análisis por Matrices de Proteínas/métodos , Administración Oral , Animales , Proteínas Sanguíneas/genética , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Regulación de la Expresión Génica/fisiología , Masculino , Ratas , Ratas WistarRESUMEN
In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol and 1% KBG, and the vitamin E group was fed standard rabbit chow containing 1% cholesterol and vitamin E (450 mg/1000 g). All four groups were kept on these diets for 8 weeks. At the end of the experiments, the percentage of surface area of the total thoracic aorta with visible plaque was significantly reduced in the OGT and KBG groups. The serum thiobarbituric acid reactive substances of the vitamin E group showed a significantly low value compared with the control group, whereas the serum lipid peroxide levels of the OGT and KBG groups were considerably lower than that of the control groups as well as that of the vitamin E group. Furthermore, the urinary 8-hydroxydeoxyguanosine levels of the OGT and KBG groups were considerably lower than that of the vitamin E group. These results suggest that OGT and KBG prevent the progression of atheromatous plaque by creating a sounder antioxidant defense system than vitamin E.
Asunto(s)
Arteriosclerosis/prevención & control , Dieta Aterogénica , Medicamentos Herbarios Chinos/uso terapéutico , Hipercolesterolemia/prevención & control , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/patología , Arteriosclerosis/patología , Progresión de la Enfermedad , Medicamentos Herbarios Chinos/farmacología , Hipercolesterolemia/patología , Masculino , Conejos , Vitamina E/uso terapéuticoRESUMEN
Previously, we revealed that oral administrations of Choto-san, a Kampo formula, and the hooks and stems of Uncaria sinensis Haviland (Rubiaceae), a medicinal plant comprising Choto-san, enhanced superoxide anion and hydroxyl radical scavenging activities in the hippocampus, and prevented delayed neuronal death of pyramidal cells in the hippocampal CA1 region in a transient forebrain ischemia gerbil model. In the present study, for the purpose of clarifying whether the endogenous antioxidant enzymes contribute to these mechanisms, we investigated the effects of Choto-san extract (CSE) and Uncaria sinensis extract (USE) on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the brain by using the same experimental model. 1.0% CSE or 3.0% USE were dissolved in water and provided to gerbils ad libitum from 7 days prior to ischemia/reperfusion (i/rp). Seven days of continuous administrations of CSE or USE without i/rp procedure enhanced CAT activity but not SOD and GSH-Px activities in both the hippocampus and cortex. CSE elevated CAT activity in the hippocampus at 7 days and in the cortex at 3h after i/rp. USE raised CAT activity in both the hippocampus and cortex at 3 h and 7 days after i/rp. These results suggest that one of the mechanisms of the protective effects of CSE and USE against transient brain ischemia-induced neuronal damage may be their enhancing effect on CAT activity in the brain.
Asunto(s)
Antioxidantes/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/enzimología , Medicamentos Herbarios Chinos/uso terapéutico , Prosencéfalo/enzimología , Uncaria , Animales , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Gerbillinae , Masculino , Tallos de la Planta , Prosencéfalo/irrigación sanguínea , Prosencéfalo/efectos de los fármacosRESUMEN
To investigate the effect of gamma-aminobutyric acid (GABA) on acute renal failure, we used a rat model of acute tubular necrosis induced by glycerol. After deprivation of water for 6h, the rats received an injection of 50% glycerol into the muscle of the rear limb at 10 ml/kg body weight. GABA was then administered orally to the rats (100 or 500 mg/kg body weight/day) once every 12h for 3 days. The rats with acute renal failure showed arrested body weight gain and an increase of kidney weight, whereas oral administration of GABA attenuated the physiological changes induced by acute renal failure. However, GABA administration had no significant effect on increased urine volume. Oral administration of GABA at a dose of 100 or 500 mg/kg body weight/day for 3 days significantly improved the markedly elevated levels of blood urea nitrogen and creatinine and the reduced creatinine clearance related to progression of renal failure. Moreover, the rats with acute renal failure exhibited high levels of fractional excretion of sodium (FE(Na)) due to alteration of tubule function following injection of glycerol. However, administration of GABA lowered the FE(Na) levels dose-dependently. Furthermore, urine osmolarity was markedly reduced in control rats with acute renal failure as compared with normal rats, whereas it was significantly increased by administration of GABA at a dose of 500 mg/kg body weight/day. These results indicate that GABA has potential as a therapeutic agent against the renal damage involved in acute renal failure.
Asunto(s)
Lesión Renal Aguda/prevención & control , Glicerol/antagonistas & inhibidores , Ácido gamma-Aminobutírico/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/fisiopatología , Animales , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Creatinina/orina , Hemólisis/fisiología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Sodio/sangre , Sodio/orina , Urodinámica/efectos de los fármacosRESUMEN
To investigate the effects of Hachimi-jio-gan on diabetic nephropathy, we employed an animal model, rats subjected to sub-total nephrectomy followed by streptozotocin injection, and administered Hachimi-jio-gan orally at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. The administration of Hachimi-jio-gan reduced dose-dependently the elevated blood glucose and urinary protein excretion levels in rats with diabetic nephropathy over the experimental period, whereas it increased creatinine clearance significantly, suggesting that Hachimi-jio-gan would prevent or delay the progression of diabetic nephropathy. In addition, the serum glycosylated protein and urea nitrogen levels were markedly elevated in rats with diabetic nephropathy compared with normal rats, and were significantly reduced by the administration of Hachimi-jio-gan, whereas Hachimi-jio-gan reversed the decrease in the serum albumin level. The serum triglyceride and total cholesterol concentrations were reduced by Hachimi-jio-gan, implying that Hachimi-jio-gan would improve the metabolic disorder of lipids caused by diabetic nephropathy. Moreover, Hachimi-jio-gan inhibited lipid peroxidation in the serum and kidney, which suggests that Hachimi-jio-gan would ameliorate oxidative stress associated with diabetic nephropathy. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were also normalized by the administration of Hachimi-jio-gan through decreases in advanced glycation end-product formation and sorbitol levels in the kidney. Hachimi-jio-gan protected against the development of renal lesions, glomerular sclerosis, tubulointerstitial lesions, mesangial matrix expansion and arteriolar sclerosis, estimated by histopathological evaluation and scoring. This study suggests that Hachimi-jio-gan may be a novel therapeutic approach to improving diabetic nephropathy.
Asunto(s)
Nefropatías Diabéticas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Administración Oral , Animales , Glucemia , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Creatinina/metabolismo , Creatinina/orina , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Productos Finales de Glicación Avanzada/metabolismo , Productos Finales de Glicación Avanzada/orina , Riñón/irrigación sanguínea , Riñón/química , Riñón/patología , Masculino , Malondialdehído/sangre , Proteinuria , Ratas , Ratas Wistar , Sorbitol/sangre , EstreptozocinaRESUMEN
Methylguanidine (MG) is widely recognized as a strong uremic toxin. The hydroxyl radical (*OH) specifically plays an important role in the pathway of MG production from creatinine (Cr). In this study, we investigated whether oral administration of (-)-epigallocatechin 3-O-gallate (EGCg) suppresses MG production in rats with chronic renal failure after intraperitoneal Cr injection. MG production from Cr was significantly increased in rats with adenine-induced renal failure, which was more vulnerable to oxidative stress, compared with that in normal rats. However, oral administration of EGCg 30 min before and after Cr injection effectively inhibited MG production. Our findings suggest that EGCg, an excellent antioxidant from green tea, exerts protective activity in rats with chronic renal failure, resulting in suppression of Cr oxidation influenced by *OH.