RESUMEN
The pathogenesis of diabetic nephropathy (DN) involves cellular activation of oxidative stress and inflammation. Eriodictyol is a citrus-derived flavonoid with multiple pharmacological and protective effects in various conditions. The protective role of Eriodictyol against diabetes and diabetic nephropathy is less investigated. The current research aimed to explore the role of eriodictyol in protecting against DN prompted by streptozotocin in male rats and investigate some possible mechanisms of action. Diabetes was brought about in rats by an i.p injection of a lone dose (65 mg/kg). Five groups of rats were included (n = 8 each) as control (non-diabetic), eriodictyol (20 mg/kg, orally), STZ-diabetic, STZ + eriodictyol (20 mg/kg, orally), and STZ + eriodictyol (20 mg/kg, orally) + ML385 (30 µg/kg, i.p.). Kidney histology and the levels of some markers of kidney function, renal oxidative stress, and renal inflammation were analyzed in all groups of rats. Treatment with eriodictyol prevented the damage in the renal glomeruli and tubules and reduced renal immune cell infiltration in STZ-treated animals. It also spiked urinary creatinine excretion and reduced urine volume and urinary levels of albumin, monocyte chemoattractant protein 1 (MCP-1), urinary kidney injury molecule-1 (KIM-1), and nephrin in these diabetic rats. In addition, eriodictyol stimulated the nuclear protein accumulation of Nrf2 and boosted the expression of superoxide dismutase (SOD), glutathione (GSH), heme oxygenase-1 (HO-1), and catalase (CAT) in the diabetic rat kidneys. In concomitance, it reduced the nuclear levels of NF-κB and levels of interleukine-6 (IL-6), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) and attenuated the reduction in renal ATP levels and the increase in the mitochondria transition pore opening (mtTPT). However, the administration of eriodictyol did not affect rats' body weights and fasting glucose and insulin levels but significantly reduced serum levels of cholesterol, triglycerides, LDL-c, and oxidized LDL-c (ox-LDL-c). In conclusion, eriodictyol prevents STZ-induced nephropathy by a hypolipidemic effect and concomitant antioxidant and anti-inflammatory effects mediated by activating Nrf2/NF-κB/antioxidant axis.
RESUMEN
Beta-caryophyllene (BCP), a cannabinoid 2 (CB2) receptor agonist has recently been found to have cardioprotective activity as an anti-inflammatory and antioxidant molecule. L-arginine (LA), a nitric oxide (NO) donor, is a potential regulator of cardiovascular function. Considering the role of CB2 receptor activation and NO regulation in cardiovascular diseases, the combination of BCP with LA may be a possible treatment of diabetic cardiomyopathy (DCM). Hence, we investigated the efficacy of the novel combination of BCP with LA on cardiovascular inflammation and oxidative stress in diabetic rats. DCM was induced by streptozotocin (55 mg/kg) in Sprague-Dawley rats intraperitoneally. BCP, LA, and BCP with LA were administered to diabetic rats for 4 weeks. After completion of the study, hemodynamic parameters, biochemical parameters, and inflammatory cytokine levels were analyzed. Also, oxidative stress parameters, nuclear factor kappa beta (NF-ĸß) expression, and histopathology in cardiac tissues were estimated. The combination of BCP (200 mg/kg) with LA (200 mg/kg) significantly normalized the hemodynamic parameters and decreased the glucose, cardiac markers, interleukin-6, and tumor necrosis factor-alpha levels. Treatment of BCP and LA showed a significant decrease in oxidative stress and downregulated the cardiac expression of NF-ĸß. Thus, the combination of BCP with LA improves cardiac functions by attenuating inflammation through NF-Ä¸ß inhibition in DCM.
Asunto(s)
Arginina/uso terapéutico , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/genética , Regulación hacia Abajo/efectos de los fármacos , FN-kappa B/metabolismo , Sesquiterpenos Policíclicos/uso terapéutico , Receptor Cannabinoide CB2/agonistas , Animales , Arginina/farmacología , Diabetes Mellitus Experimental , Quimioterapia Combinada , Masculino , Estrés Oxidativo/efectos de los fármacos , Sesquiterpenos Policíclicos/farmacología , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
Abstract The present study aims to examine the anti-diabetic effects of fullerene C60 nanoparticle, as an anti-oxidant compound, on serum glucose level, body weight, food and water intake, and pancreatic oxidative stress in the rats with type 1 diabetes. Diabetes mellitus was induced by single intravenous injection of streptozotocine (45 mg/kg) into the tail vein of the rats. Four groups of rats were divided as follow: normal, normal treatment, diabetic, and diabetic treatment groups. Normal treatment and diabetic treatment groups received intra-orally fullerene (1 mg/ kg/daily) up to day 60 following streptozotocine injection. Oxidative stress markers in the pancreas were evaluated on day 60 after inducing diabetes mellitus. Injection of streptozotocine significantly increased serum glucose level as well as food and water intake on all experimental days; it decreased body weight on day 60. Streptozotocine increased MDA level and decreased GSH level and SOD activity in the pancreas. Fullerene significantly decreased food and water intake and increased body weight as compared with the diabetic group. Fullerene also could normalize the pancreatic MDA and GSH markers. The present study suggested that fullerene can decrease diabetic symptoms via its anti-oxidant activity in the pancreas in the rats with type 1 diabetes mellitus.
RESUMEN
An in vivo intestinal perfusion model was used to investigate how experimental hyperglycemia affects intestinal elimination and biliary excretion in the rat. Experimental diabetes was induced by administration of streptozotocin (65 mg/kg, i.v.). The intestinal perfusion medium contained 250 µM (±)-ibuprofen. An isocratic high-performance liquid chromatography method with UV-visible detection was developed to quantitate ibuprofen in the intestinal perfusate, while a gradient method was applied to quantitate ibuprofen and ibuprofen-ß-d-glucuronide in the bile. The limit of quantitation of ibuprofen was found to be 0.51 µM in the perfusate of the small intestine. In the bile, the limit of quantitation of ibuprofen and ibuprofen-ß-d-glucuronide was 4.42 and 10.3 µM, respectively. Unconjugated ibuprofen and ibuprofen-ß-d-glucuronide were detected in the bile; however, no ß-d-glucuronide of ibuprofen could be detected in the intestinal perfusate. The results indicate that experimental diabetes can cause a decrease in the disappearance of ibuprofen from the small intestine. Excretion of both ibuprofen and ibuprofen-ß-d-glucuronide decreased to the bile in experimental diabetes. The results can be explained by the results of molecular biological studies indicating streptozotocin-initiated alterations in the intestinal and hepatic transport processes.
Asunto(s)
Eliminación Hepatobiliar , Hiperglucemia/metabolismo , Ibuprofeno/farmacocinética , Eliminación Intestinal , Animales , Masculino , Ratas , Ratas WistarRESUMEN
CONTEXT: Oxidative stress plays an important role in development of diabetes mellitus. Satureja bachtiarica Bunge (Lamiaceae) is a rich source of bioactive compounds with antioxidant properties. OBJECTIVE: This study investigates the antidiabetic effect of hydroalcoholic extract of aerial parts of S. bachtiarica. METHODS AND MATERIALS: Male Wistar rats were randomly divided into six groups (n = 8) including control (normal saline), diabetic [Streptozotocin (STZ)], intervention (STZ plus hydroalcoholic extract of S. bachtiarica at doses of 75, 150 and 250 mg/kg/d) and positive control (STZ plus captopril 50 mg/kg/d) groups. A single intraperitoneal (IP) injection of STZ (60 mg/kg) was used to induce diabetes and IP therapy with drugs was performed for four weeks. RESULTS: In diabetic rats, serum total antioxidant capacity (TAC) decreased significantly, but glucose, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT) and malondialdehyde (MDA) increased significantly as compared to the control (p < 0.05). Treatment with extract (250 mg/kg) caused a significant decline in serum glucose, GGT, ALT, AST and MDA as well as a significant increase in serum TAC (p < 0.05). During the intervention period, diabetic rats showed significant weight loss, but extract (250 mg/kg) treated rats did not show any weight loss. Extract (250 mg/kg) up-regulated GLUT2 expression and down-regulated GLUT4 expression in the liver (p < 0.05). S. bachtiarica extract at all dosage levels prevented STZ-induced histological damage of liver, kidney and pancreas. DISCUSSION AND CONCLUSIONS: S. bachtiarica extract exhibits antidiabetic effects through modulation of oxidative stress and expression of GLUT2 and GLUT4.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 4/genética , Hipoglucemiantes/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Satureja/química , Animales , Compuestos de Bifenilo/química , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/genética , Etanol/química , Expresión Génica/efectos de los fármacos , Hipoglucemiantes/aislamiento & purificación , Masculino , Picratos/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/aislamiento & purificación , Ratas Wistar , Estreptozocina , Agua/químicaRESUMEN
Diabetes is one of the leading diseases worldwide and, thus, finding new therapeutic alternatives is essential. The development of non-alcoholic fatty liver disease is a notable diabetic complication. Therefore, antioxidant therapy became a leading topic in the world of diabetes research. The objective of this present study was to evaluate the effects of antioxidant N-acetylcysteine (NAC) administration on serum biochemical parameters and oxidative stress parameters in hepatic tissue of the diabetic rats. Thirty-two animals were divided in 4 groups (n = 8): G1, normal rats; G2, normal rats + NAC; G3, diabetic rats; and G4, diabetic rats + NAC. Diabetes was induced in diabetic groups through streptozotocin. NAC administration was effective in improving hyperglycemia and hypoinsulinemia, as well as reducing serum alanine-aminotransferase and urea, hepatic triglycerides accumulation, and oxidative stress biomarkers in the diabetic liver, as well as improving the activity of hepatic antioxidant enzymes. This effect was likely due to NAC's ability of restoring intracellular glutathione, an important compound for the antioxidant defense, as well as due to NAC's direct antioxidant properties. Thus, NAC administration was useful for reducing hepatic oxidative stress and decreased the deposit of triacylglycerols, minimizing diabetic hepatic damage, making it a promising therapeutic adjuvant in the future.
Asunto(s)
Acetilcisteína/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Estrés Oxidativo , Acetilcisteína/farmacología , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Ácidos Grasos/metabolismo , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Insulina/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Estreptozocina , Triglicéridos/metabolismo , Urea/sangreRESUMEN
Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg-1·day-1) or NTZ (200 mg·kg-1·day-1) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , PPAR gamma/metabolismo , Animales , Glucemia/metabolismo , Tamaño Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Ayuno/sangre , Regulación de la Expresión Génica/efectos de los fármacos , Resistencia a la Insulina , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/fisiopatología , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Diabetes mellitus, besides having deleterious effects, induces cardiac adaptation that may reduce the heart's susceptibility to ischemia-reperfusion (IR) injury. This study aimed to investigate whether changes in mitochondrial properties are involved in the mechanisms of increased resistance of the diabetic heart to IR. Adult male Wistar rats were made diabetic by a single dose of streptozotocin (65 mg·kg-1, i.p.), and on the day 8, Langendorff-perfused hearts were subjected to 30 min global ischemia and 40 min reperfusion. Baseline preischemic parameters in the diabetic hearts did not differ markedly from those in the nondiabetic controls, except for lower left ventricular developed pressure, higher mitochondrial membrane fluidity, and protein levels of manganese superoxide dismutase. On the other hand, diabetic hearts showed significantly better post-IR functional restoration and reduced arrhythmogenesis associated with lower reactive oxygen species production as compared with healthy controls. IR decreased membrane fluidity in both experimental groups; however, it led to a complete recovery of mitochondrial Mg2+-ATPase activity in diabetics in contrast to its reduction in nondiabetics. These findings indicate that the heart may become adapted to diabetes-induced alterations that might increase its tolerance to an ischemic insult. Preserved mitochondrial function might play a role in the mechanisms of the heart's resistance to IR injury in diabetics.
Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Resistencia a la Enfermedad , Mitocondrias Cardíacas/patología , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/patología , Animales , ATPasa de Ca(2+) y Mg(2+)/metabolismo , Peroxidación de Lípido , Masculino , Fluidez de la Membrana , Mitocondrias Cardíacas/metabolismo , Membranas Mitocondriales/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Ratas , Ratas WistarRESUMEN
Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10-8 mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10-8 mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.
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Plaquetas/efectos de los fármacos , Plaquetas/fisiología , Diabetes Mellitus Experimental/fisiopatología , Kisspeptinas/farmacología , Animales , Diabetes Mellitus Experimental/metabolismo , Kisspeptinas/metabolismo , Masculino , Agregación Plaquetaria/efectos de los fármacos , Ratas , Receptores de Kisspeptina-1/metabolismo , Receptores de Neuropéptido/metabolismoRESUMEN
Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 µmol/L of spironolactone, diabetic rats treated with 0.1 µmol/L of spironolactone, healthy rats treated with 3 µmol/L of spironolactone, and diabetic rats treated with 3 µmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.
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Diabetes Mellitus Experimental/fisiopatología , Corazón/efectos de los fármacos , Corazón/fisiopatología , Espironolactona/farmacología , Animales , Circulación Coronaria/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Espironolactona/uso terapéutico , Disfunción Ventricular Izquierda/tratamiento farmacológicoRESUMEN
Diabetes mellitus is a frequent and serious metabolic illness all over the world and plants have been a desirable source of medicine recently. Diabetes has unpleasant effect on male reproductive system and it may lead to male infertility. It causes erectile dysfunction and reduces ejaculate volume by affecting the health of small blood vessels and the small nerves that control ejaculation and also decreases libido by decreasing testosterone levels. Current study evaluated the possible protective efficiency of Lepidium sativum (Garden cress) seed extract on fasting blood sugar (FBS) and then assessed histopathological change of epididymis in streptozotocine (STZ)-induced diabetic rats. We randomly categorized 50 adult male Wistar rats into five groups (each 10 rats). Group 1 was control placebo group receiving only 0.1 ml normal saline via gastric gavages, Group 2 as control diabetic rats received an intraperitoneal (IP) injection of STZ 60 mg/kg body weight. Rats with FBS >250 mg/dl were considered as diabetic. Group 3 were diabetic rats receiving insulin in dose 3U/100 g body weight and Groups 4 and 5 were diabetic rats that received 0.1 cc of 200 and 400 mg/kg, ethanol extract of Lepidium sativum seed by gavages daily. One day after the last gavages, rats were anesthetized by chloroform. Epididymis duct was removed from abdomen and weighed with a digital scale. Afterwards, samples were putted in Bouin's solution for histological measurement. Administration of 200 and 400 mg/ml doses of Lepidium sativum seed extract increased epithelium height and decreased interstitial volume density and fibro muscular thickness significantly. Also, volume density of epithelium, fibro muscular, lumen and interstitial decreased significantly. Tubular and lumen diameter did not change significantly in different groups. It appears Lepidium sativum seed extract is a beneficial protective supplementary agent against adverse effects of diabetes on male reproductive system.
La diabetes mellitus es una enfermedad metabólica frecuente y grave que afecta a los hombres en todo el mundo. Recientemente, las plantas han sido una fuente deseable de medicina para este tipo de enfermedad. La diabetes tiene un efecto perjudicial en el sistema reproductivo masculino y puede conducir a la infertilidad. Causa disfunción eréctil y reduce el volumen de la eyaculación al afectar los pequeños vasos sanguíneos y los nervios que controlan la eyaculación. También disminuye la libido reduciendo los niveles de testosterona. El presente estudio evaluó la posible eficacia protectora del extracto de semilla de Lepidium sativum en la glucemia en ayunas y también se evaluó el cambio histopatológico del epidídimo en ratas diabéticas inducidas por estreptozotocina (STZ). Se dividieron aleatoriamente 50 ratas Wistar macho adultas en cinco grupos de 10 ratas cada uno. El grupo 1 recibió 0,1 ml de solución salina normal a través de los gavajes gástricos, el grupo 2 de ratas diabéticas control recibió una inyección intraperitoneal (IP) de STZ 60 mg / kg de peso corporal. Las ratas con FBS> 250 mg / dl se consideraron como diabéticas. El Grupo 3 eran ratas diabéticas que recibieron insulina en dosis de 3 U/ 100 g de peso corporal y los Grupos 4 y 5 estaban compuestos por ratas diabéticas que recibieron 0,1 cc con 200 y 400 mg / kg, de extracto de etanol de semillas de Lepidium sativum por gavajes diarios. Un día después de los últimos gavages, las ratas fueron anestesiadas con cloroformo. Se extrajo el epidídimo y se pesó con una pesa digital. Posteriormente, las muestras se pusieron en solución de Bouin para el estudio histológico. La administración de dosis de 200 y 400 mg / ml de extracto de semilla Lepidium sativum aumentó la altura del epitelio y disminuyó significativamente la densidad volumétrica intersticial y el grosor fibromuscular. Además, la densidad volumétrica del epitelio fibromuscular, lumen e intersticio disminuyeron significativamente. El diámetro tubular y el lumen no cambiaron significativamente en los diferentes grupos. El extracto de semilla de Lepidium sativum es un agente complementario beneficioso protector contra los efectos adversos de la diabetes en el sistema reproductor masculino.
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Animales , Masculino , Ratas , Extractos Vegetales/administración & dosificación , Lepidium sativum/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Epidídimo/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Semillas , Ratas Wistar , Epidídimo/patologíaRESUMEN
Diabetes mellitus (DM) is associated with an electrical remodeling of the heart, increasing the risk of arrhythmias. However, knowledge of electrical remodeling in the sinoatrial node (SAN) by DM is limited. We investigated the expression of HCN channel isoforms, HCN1-HCN4, in SAN from streptozotocin (STZ)-induced diabetic rats and the age-matched controls. We found that the STZ-induced diabetic rats have a lower intrinsic heart rate, a lengthened sinoatrial conduction time, and rate-corrected maximal sinoatrial node recovery time in vivo as well as a longer cycle length (CL) in vitro, as compared with the control. Optical mapping of the SAN demonstrated an inferior leading pacemaker site, reduced SAN conduction velocity and diastolic depolarization slope, and a longer action potential duration in the STZ-induced diabetic rats than in the control. The transcripts and proteins of HCN2 and HCN4 in diabetic SAN were reduced. Specific blockade of HCN channels by 3 µmol/L ivabradine significantly prolonged the CL of a Langendorff heart by 18% in the diabetic rats and 26% in the control. The reduced expression of HCN channel isoforms in the SAN of the STZ-induced diabetic rat may be an important contributor to the reduced SAN function in DM.
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Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Regulación de la Expresión Génica , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Nodo Sinoatrial/metabolismo , Animales , Benzazepinas/farmacología , Diabetes Mellitus Experimental/fisiopatología , Regulación de la Expresión Génica/efectos de los fármacos , Ivabradina , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Nodo Sinoatrial/efectos de los fármacos , Nodo Sinoatrial/fisiopatologíaRESUMEN
BACKGROUND: Hyoscyamus albus L. (Solanaceae) an old medicinal plant is a rich source of tropane and nortropane alkaloids which confers to this plant a number of very interesting and beneficial therapeutic effects. PURPOSE: Calystegines that are polyhydroxylated alkaloids and imino-sugars poccess significant glycosidases inhibitory activities and are therefore good candidats for the treatment of diabetes mellitus. STUDY DESIGN: Calystegines extracted from Hyoscyamys albus seeds were tested for teir acute oral toxicity and investigated for their in-vivo antidiabetic effect on Streptozotocine induced diabetes in mice. METHODES: Calystegines were extracted from the seeds plant using an Ion exchange column; the remaining extract was then administrated orally to mice at several single doses for acute toxicity assay. A dose of 130mg/kg streptozotocine was injected to mice to induce diabetes mellitus, and diabetic mice were treated orally during 20days with 10mg/kg and 20mg/kg calystegines and 20mg/kg glibenclamide as the reference drug. RESULTS: Acute oral toxicity showed that calystegines are not toxic up to a dose of 2000mg/kg with absence of any signs of intoxication and damages in Liver and kidney tissues. The nortropane alkaloids markedly reduced blood glucose levels and lipid parameters of diabetic mice to normal concentrations after 20days of treatment at 10mg/kg and 20mg/kg (p<0.05). Histopathological study of diabetic mice pancreas indicated that calystegines of Hyoscyamus albus have minimized streptozotocine damages on ß-cells of islets of langerhans, stimulated ß-cells regeneration and improved with this insulin secretion. CONCLUSION: The findings of this study suggest that calystegines are potent antidiabetic agents with antihyperglicemic and hypolipidemic effects, and a protective fonction on pancreas in streptozotocin induced diabetes in mice.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Hyoscyamus/química , Hipoglucemiantes/uso terapéutico , Tropanos/aislamiento & purificación , Tropanos/uso terapéutico , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Modelos Animales de Enfermedad , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Femenino , Prueba de Tolerancia a la Glucosa , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Páncreas/efectos de los fármacos , Páncreas/patología , Semillas/química , Estreptozocina , Pruebas de Toxicidad Aguda , Tropanos/administración & dosificación , Tropanos/farmacologíaRESUMEN
OBJECTIVES: We evaluated the effects of S-allylcysteine (SAC) on biomarkers of the polyol pathway in streptozotocin-nicotinamide (STZ-NA)-induced diabetes in rats. METHODS: Diabetes was induced in male albino Wistar rats by intraperitoneal administration of STZ (55 mg kg-1 bw-1) and NA (110 mg kg-1 bw-1). SAC (150 mg kg-1 bw-1) was orally administered to the rats with diabetes for 45 days to assess its effects on blood glucose, insulin, insulin resistance, glycated hemoglobin, aldose reductase (AR), sorbitol dehydrogenase (SDH), sorbitol, fructose, thiobarbituric acid-reactive substances (TBARS), hydroperoxide, hemoglobin and glutathione (GSH). RESULTS: On SAC administration in the rats with diabetes, the levels of blood glucose, insulin resistance, glycated hemoglobin, AR, SDH, sorbitol, fructose, TBARS and hydroperoxide increased significantly (p<0.05), whereas those of insulin, hemoglobin and GSH decreased. SAC showed therapeutic effects similar to those of gliclazide in decreasing blood glucose, AR, SDH, sorbitol, fructose, glycosylated hemoglobin, TBARS and hydroperoxides levels and significant increases in insulin, hemoglobin and GSH activity in rats with diabetes. Moreover, histopathologic studies also revealed the protective effect of SAC on pancreatic beta cells. CONCLUSIONS: The results indicate that SAC prevents complications of diabetes by reducing the influx of glucose in the polyol pathway, thereby elevating the GSH level and reducing the activities of AR and SDH. Therefore, SAC may have imperative implications for the deterrence and early treatment of type 2 diabetes.
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Cisteína/análogos & derivados , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Redes y Vías Metabólicas/efectos de los fármacos , Polímeros/metabolismo , Aldehído Reductasa/sangre , Animales , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Cisteína/farmacología , Cisteína/uso terapéutico , Fructosa/sangre , Glutatión/sangre , Hemoglobina Glucada/metabolismo , Hemoglobinas/metabolismo , Peróxido de Hidrógeno/sangre , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , L-Iditol 2-Deshidrogenasa/sangre , Ratas Wistar , Sorbitol/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.
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Encéfalo/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Flavonoides/farmacología , Hígado/efectos de los fármacos , Páncreas/efectos de los fármacos , Estreptozocina/farmacología , Animales , Antioxidantes/metabolismo , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Encéfalo/metabolismo , Catalasa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutatión Transferasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Páncreas/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved.
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Aorta Torácica/efectos de los fármacos , Aorta/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Endotelio Vascular/efectos de los fármacos , Estreptozocina/farmacología , Acetilcolina/farmacología , Animales , Aorta/metabolismo , Aorta Torácica/metabolismo , Femenino , Masculino , NADH NADPH Oxidorreductasas/metabolismo , NADPH Oxidasa 1 , NADPH Oxidasas/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fenilefrina/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190-220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.
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Diabetes Mellitus Experimental/metabolismo , Membrana Eritrocítica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Sesbania/química , Animales , Masculino , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
BACKGROUND: Propolis is an organic resinous viscous substance collected from flower bud and plant sprig by bees. Propolis has a potential treatment agent for oxidative damage caused by diabetes in hippocampus due to its flavonoid and phenolic content. AIM: In this study effect of propolis on thiobarbituric acid reactive substances and anti-oxidative enzyme levels of hippocampus in diabetic rats induced by streptozotocin was investigated. MATERIALS AND METHODS: The study involved measuring levels of SOD, CAT, GSH-Px and TBARs in hippocampus tissue of STZ-induced diabetic rats (Adult Male Sprague Dawley rats) after applying propolis for one month. The subjects of the study were composed of 51 rats randomly assigned to four groups (Control, STZ, P+STZ and STZ+P). For analysis of data, Kruskal Wallis Test was utilized. RESULTS: The findings of the study showed that there were no significant difference in the levels of TBARS, SOD, CAT and GSH-Px of hippocampus across the groups. CONCLUSION: Propolis application in four-week duration does not have effect on TBARS, SOD, CAT and GSH-Px levels of hippocampus of diabetic rats. These findings mean that more time for observing oxidative harms on hippocampus is needed.
RESUMEN
This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.
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Antidepresivos/uso terapéutico , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hesperidina/uso terapéutico , Animales , Antidepresivos/farmacología , Monoaminas Biogénicas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/psicología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/psicología , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Glutatión/metabolismo , Hesperidina/farmacología , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , EstreptozocinaRESUMEN
OBJECTIVE: Fenugreek and its active compound diosgenin are ancient herbal medicines recommended by the World Health Organization. In this study, the effect of diosgenin on changes in carbohydrate metabolic enzymes and glycogen content in muscle and kidneys of streptozotocin-induced diabetes rats were evaluated. METHODS: Diabetes was induced in male albino Wistar rats by intraperitoneal administration of streptozotocin. The diosgenin at different doses (15, 30 and 60 mg/kg body weight) was administered orally to normal and streptozotocin-diabetic rats for 45 days. RESULTS: Streptozotocin intoxication led to a significant increase (p<0.05) in blood glucose and a decrease in insulin levels. The carbohydrate metabolic enzymes and glycogen content were also altered. The daily oral administration of diosgenin at different doses (15, 30 and 60 mg/kg body weight) to diabetic rats for 45 days resulted a significant (p<0.05) decline in blood glucose level and a significant increase in plasma insulin level. The altered activities of carbohydrate metabolic key enzymes in muscle and kidneys of diabetic rats were significantly (p<0.05) reverted to near normal level by the administration of diosgenin. The obtained results were compared with glibenclamide, a standard oral hypoglycemia drug. CONCLUSIONS: The modulatory effects of diosgenin on attenuating the activities of carbohydrate metabolic enzymes afford a promise for persistent use for the treatment of diabetes in the future, even though clinical studies to evaluate this possibility may be warranted.