Eucommia lignans alleviate the progression of diabetic nephropathy through mediating the AR/Nrf2/HO-1/AMPK axis in vivo and in vitro / 中国天然药物

Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.

Acacia senegal inhibits diabetic nephropathy ultrastructure alteration and renal biomarkers changes in rats / Acacia senegal inhibe la alteración de la ultraestructura de la nefropatía diabética y los cambios en los biomarcadores renales en rata

SUMMARY: Diabetic nephropathy (DN) is the most common complication of diabetes. Several studies have been done in a trial to protect against this problem at the ultrastructure level. This study investigates the protective effect of oral administration of Acacia senegal (AS) against the development of DN. Sixty male albino rats were randomly divided into six groups: control, Acacia senegal control, Diabetic untreated, diabetic insulin-treated, Diabetic AS treated, and Diabetic insulin and AS combined treated groups. Plasma glucose, HbA1c, serum Albumin, creatinine, urine creatinine was measured using specific kits. Determinations of creatinine clearance and blood pressure were done. The renal tissues of both kidneys were prepared to investigate under both light (LM) and electron microscope (EM). Ultrastructure examination of renal rats tissue of diabetic untreated rats showed the destruction of the glomerular basement membrane and endothelial cells together with hemorrhage in glomerular capsules (Bowman's capsules). On the other side, both LM and EM revealed improving the endothelial cells and the other glomerular capsules structures, especially with the combined treated group, which confirmed the improvement of the biochemical investigation in the study. In conclusion, from the present study, using the oral AS together with SC insulin could be protected against the development of DN.

RESUMEN: La nefropatía diabética (ND) es la complicación más común de la diabetes. Se han realizado varios estudios de ensayo para abordar esta dificultad a nivel de ultraestructura. Este estudio investiga el efecto protector de la administración oral de Acacia senegal (AS) contra el desarrollo de la ND. Se dividieron sesenta ratas albinas machos aleatoriamente en seis grupos: control, control de Acacia senegal, diabéticos no tratados, diabéticos tratados con insulina, diabéticos tratados con AS y grupos tratados con compuesto de insulina diabética + AS. Se midieron utilizando kits específicos, glucosa plasmática, HbA1c, albúmina sérica, creatinina en sangre y en orina. Se registraron la creatinina y la presión arterial. Los tejidos renales de ambos riñones se prepararon para investigar tanto con microscopio óptico (MO) como electrónico (ME). El examen de la ultraestructura del tejido renal de ratas diabéticas no tratadas mostró la destrucción de la membrana basal glomerular y las células endoteliales junto con hemorragia en las cápsulas glomerulares (cápsulas de Bowman). Por otro lado, tanto MO como ME revelaron una mejora de las células endoteliales y las estructuras capsulares glomerulares, en el grupo tratado con el compuesto, lo que confirmó la mejora de la investigación bioquímica. En conclusión, el uso de AS oral en combinación con insulina podría proteger contra el desarrollo de ND.

Preventive role of gum Arabic administration on STZ induced diabetic kidney disease in rats; renal antioxidant and histopathological evidence / Función preventiva de la administración de goma arábiga en la enfermedad renal diabética inducida por STZ en ratas; antioxidante renal y evidencia histopatológica

This study was set to investigate the effect of gum Arabic (G.A.) on diabetic kidney disease. We divided sixty male Sprague rats randomly into six groups. Normal control, normal rats treated with G.A., untreated diabetic rats, diabetic rats treated with insulin, diabetic rats treated with G.A., and diabetic rats treated with both insulin and G.A. Diabetes was induced by a single intraperitoneal injection of STZ. Forty eight hr post injections. Insulin was injected subcutaneously (1.6/IU/100g/day). We provided G.A. in drinking water (10 %w/ v).). At the end of the twelve weeks, blood was drawn for measurement of blood glucose, glycosylated hemoglobin (HbA1C), serum lipids, serum creatinine, and blood urea. Renal tissue oxidative stress (O.S.) was assessed by measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the concentrations of reduced glutathione (GSH) and malondialdehyde (MDA). For histological assessments, sections from segments of kidneys were processed and stained with hematoxylin and eosin (H&E) for assessment under the light microscope. STZinduced diabetes caused an elevation of blood glucose, HbA1c, urea and creatinine, triglycerides LDL and cholesterol, MDA with reduction of HDL, GSH level, and CAT and SOD activities. Histologically, kidneys from diabetic rats showed marked glomerular and tubular changes. Administration of G.A. alone to diabetic rats had a significant hypoglycemic, hypolipidemic, and antioxidant effect, although the levels achieved remained significantly abnormal compared with the untreated group with no effect on urea and creatinine levels. Co-administration of G.A. with insulin reversed the impact of D.M. on all parameters evaluated including the histological changes and led to normal urea and creatinine levels. We concluded that G.A., in combination with insulin, improves chemically-induced diabetes and its renal complications, possibly by modulation of oxidative stress.

En este estudio se evaluó el efecto de la goma arábiga (GA) en la enfermedad renal diabética. Dividimos sesenta ratas macho Sprague Dawley al azar en seis grupos. Control normal, ratas normales tratadas con GA, ratas diabéticas no tratadas, ratas diabéticas tratadas con insulina, ratas diabéticas tratadas con GA y ratas diabéticas tratadas con insulina y GA. La diabetes fue inducida por una sola inyección intraperitoneal de STZ. Cuarenta y ocho horas después se inyectó insulina por vía subcutánea (1,6 / UI / 100 g / día). A los animales se les dió GA en agua potable (10 % p / v)). Al final de las doce semanas, se extrajo sangre para medir la glucosa, la hemoglobina glicosilada (HbA1C), los lípidos en suero, la creatinina en suero y la urea en sangre. El estrés oxidativo del tejido renal (SO) se evaluó midiendo las actividades de la enzima superóxido dismutasa (SOD) y la catalasa (CAT), y las concentraciones de glutatión reducido (GSH) y malondialdehído (MDA). Para las evaluaciones histológicas, se procesaron secciones de segmentos de riñones y se tiñeron con hematoxilina y eosina (H & E) para análisis bajo microscopio óptico. La diabetes inducida por STZ causó una elevación de la glucosa en sangre, HbA1c, urea y creatinina, triglicéridos LDL y colesterol, MDA con reducción de las actividades de HDL, GSH y CAT y SOD. Histológicamente, los riñones de ratas diabéticas mostraron marcados cambios glomerulares y tubulares. La administración de GA solo en las ratas diabéticas tuvo un efecto hipoglucémico, hipolipidémico y antioxidante significativo, aunque los niveles alcanzados permanecieron significativamente anormales en comparación con el grupo no tratado, sin ningún efecto sobre los niveles de urea y creatinina. La dministración conjunta de GA con insulina revirtió el impacto de DM en todos los parámetros evaluados, incluidos los cambios histológicos y condujeron a niveles normales de urea y creatinina. Concluimos que GA en combinación con insulina, mejora la diabetes inducida químicamente y sus complicaciones renales, posiblemente mediante la modulación del estrés oxidativo.

SGLT-2 inhibitors in diabetes: a focus on renoprotection

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.

An experimental study of exenatide effects on renal injury in diabetic rats

Abstract Purpose: To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats. Methods: Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined. Results: Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05). Conclusions: Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.

Características clínicas de los pacientes diabéticos que acuden por primera vez a una consulta nefrológica en hospitales públicos de Lima / Clinical characteristics of diabetic patients attending for the first time a nephrologic consultation in Lima public hospitals

Introducción: La diabetes mellitus es la principal causa de enfermedad renal crónica y se recomienda una referencia temprana al nefrólogo, ya que se ha reportado peores resultados en pacientes con referencia tardía. Objetivos: Determinar las características de los pacientes diabéticos en su primera consulta nefrológica. Diseño: Estudio multicéntrico, observacional y analítico. Lugar: Hospital Nacional 2 de Mayo, Hospital Nacional Arzobispo Loayza, Hospital Daniel Alcides Carrión y Hospital María Auxiliadora. Participantes: Pacientes diabéticos. Intervenciones: Se estudió a los pacientes en su primera consulta nefrológica entre septiembre 2011 y febrero 2012. Para la descripción se utilizó porcentajes, frecuencias y desviaciones estándar. Principales medidas de resultados: Características clínicas de los pacientes diabéticos. Resultados: Se estudió 200 pacientes diabéticos, con tiempo de diagnóstico promedio de 12,9 años. El 73 por ciento recibió educación para autocuidados. El 40 por ciento refería que no tomaba sus medicamentos y 57 por ciento no seguía su dieta regularmente. El 70 por ciento era hipertenso con tiempo de diagnóstico promedio de 4,2 años; 36,5 por ciento era obeso, 52,8 por ciento sufría de dislipidemia, 10,5 por ciento tenía antecedente de enfermedad cardiovascular. El 81,5 por ciento refería no haber tenido una evaluación previa de la función renal. El 39,5 por ciento tenía hemoglobina glicosilada (HbA1c) >7 por ciento, 48,5 por ciento colesterol >200 mg/dL, 54,5 por ciento cLDL>100 mg/dL y 46,5 por ciento triglicéridos >150 mg/dL; 57 por ciento un tiempo de filtración glomerular<60 mL/min y 37 por ciento presentó albuminuria de 300 mg/d o más. Conclusiones: Casi la mitad de los pacientes no seguía las recomendaciones de autocuidados. Debido a los factores de riesgo cardiovascular involucrados en este grupo, se debería reforzar su educación.

Introduction: Diabetes mellitus is the leading cause of chronic renal disease; early referral to the nephrologist is recommended as the outcome is worse in patients with late referral. Objectives: To determine clinical characteristics of diabetic patients upon their first nephrologic consultation. Design: Multicenter, observational and analytical study. Setting: Hospital Nacional 2 de Mayo, Hospital Nacional Arzobispo Loayza, Hospital Daniel Alcides Carrion and Hospital Maria Auxiliadora. Participants: Diabetic patients. Interventions: Diabetic patients were studied between September 2011 and February 2012. Percentages were used to describe frequencies and standard deviations. Main outcome measures: Clinical characteristics of diabetes patients. Results: From 200 diabetic patients with 12.9 years mean time to diagnosis 73 per cent had received education for self-care, 40 per cent reported not taking their medications and 57 per cent did not follow a regular diet; 70 per cent were hypertensive with 4.2 years average from time of diagnosis, 36.5 per cent were obese, 52.8 per cent had dyslipidemia; 10.5 per cent had a history of cardiovascular disease, and 81.5 per cent reported no prior assessment of renal function; 39.5 per cent had glycated hemoglobin (HbA1c) >7 per cent, 48.5 per cent cholesterol >200 mg/dL, 54.5 per cent LDLc >100 mg/dL, and 46.5 per cent triglycerides >150 mg/dL. Fifty seven per cent had a glomerular filtration rate <60 mL/min, and 37 per cent albuminuria 300 mg/d or more. Conclusions: Almost half of all patients did not follow self-care recommendations. Due to substantial cardiovascular risk factors involved, education of this group should be strengthened.

Efecto de la administración de espironolactona sobre la pérdida de podocitos y la progresión de la nefropatía diabética experimental / Effects of spironolactone administration on the podocytes loss and progression of experimental diabetic nephropathy

Objetivos. Evaluar el efecto de espironolactona (SPL) sobre la pérdida de los podocitos durante la progresión de la nefropatía diabética (ND) experimental. Materiales y métodos. Aleatoriamente un grupo de ratas macho Holtzman recibieron estreptozotocina (grupo diabético) o citrato buffer (grupo control). Las ratas diabéticas fueron tratadas con SPL (50 mg/kg/día). El área glomerular y la celularidad fueron evaluadas por métodos histomorfométricos. La lesión y pérdida de podocitos fue evaluada por la expresión de desmina y Wt-1, respectivamente. La expresión génica del TGF-β1 se evaluó mediante RT-PCR. Resultados. Los niveles de glucosa, el área glomerular, la expansión mesangial y el contenido de colágeno se incrementaron significativamente en las ratas diabéticas. La administración de SPL previno estos cambios sin modificar los niveles de glucosa. La inmunotinción para Wt-1 se redujo significativamente, mientras que la inmunotinción para desmina se incrementó drásticamente en las ratas diabéticas. El tratamiento con SPL previno el incremento de expresión de desmina y la pérdida de expresión de Wt-1. Asimismo, la administración de SPL previno el incremento de la expresión del mRNA del TGF-β1 en las ratas diabéticas. Conclusiones. El tratamiento con SPL, a través de efectos glucosa independientes, atenúa la perdida de podocitos y la progresión de los cambios morfológicos de la ND. Los presentes resultados sugieren que estos efectos son mediados, al menos en parte, por la inhibición de la la expresión del mRNA del TGF-β1.

Objectives. Evaluate the effect of spironolactone (SPL) on the loss of podocytes during the progression of experimental diabetic nephropathy (DN). Materials and methods. A group of male Holtzman rats randomly received streptozotocin (diabetic group) or a buffer citrate (control group). Diabetic rats were treated with SPL (50 mg/kg/day). The glomerular area and the cellularity were evaluated by histomorphometric methods. The injury and loss of podocytes was assessed by desmin expression and Wt-1, respectively. The gene expression of TGF-β1 was assessed by RT-PCR. Results. Glucose levels, the glomerular area, the mesangial expansion and collagen content increased significantly in diabetic rats. The administration of SPL prevented these changes without changing glucose levels. Immunostain for Wt-1 decreased significantly while immunostain for desmin increased dramatically in diabetic rats. Treatment with SPL prevented the increase of desmin expression and the loss of Wt-1 expression. Furthermore, the administration of SPL prevented the increase of TGF-β1 mRNA expression in diabetic rats. Conclusions. Treatment with SPL, through independent glucose effects, reduces the loss of podocytes and the progression of DN morphological changes. These results suggest that these effects are mediated, at least in part, by the inhibition of TGF-β1 mRNA expression.

Hypolipidemic effect of aqueous extract of Carum carvi [black Zeera] seeds in diet induced hyperlipidemic rats

Medicinal plants play a key role in preventing various diseases. Hyperlipidemia is a major contributor to the pathogenesis of cardiovascular diseases. The purpose of the present study was to assess the effect of aqueous extract of Carum carvi seeds in diet induced hyperlipidemia in rats. 2% cholesterol diet were given to rats for six weeks and rats showed high lipid levels were included in the study. Then all rats were divided into, normal control group [A], hyperlipidemia positive control group [B], and the remaining two groups [C and D] served as experimental groups. Group C hyperlipidemic experimental rats received aqueous dried extract of Carum carvi seeds at 60 mg/kg of body weight for eight weeks on daily basis. On the other hand group D rats received simvastatin at 1.0 mg/kg body weight for eight weeks. Blood samples were collected after eight weeks. The hyperlipidemic positive control group rats showed variable increase in serum triglycerides, LDL and total cholesterol levels. Serum HDL levels decreased in hyperlipidemic positive control groups. Carum carvi and simvastatin significantly decreased the levels of these parameters in rats. On comparison Carum carvi reduced lipid levels more, effectively than the simvastatin. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity which might be involved in hypolipidemia. In conclusion, Carum carvi aqueous seeds extract decrease lipid levels in diet induced hyperlipidemic rats

MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN), a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs). The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

Vitamin E ameliorates renal damage in streptozotocin induced diabetes in albino rats

This study was designed to find out the role of Vitamin E on serum glucose and Creatinine concentrations of male albino rats made diabetic by streptozotocin. Prospective study. This study was conducted at the Department of Physiology; Basic Medical Sciences Institutes [BMSI], Jinnah post Graduate Medical Center [JPMC], Karachi from Feb. 2010 to March 2010. In a 4 weeks study, 45 male albino rats were divided into 3 groups containing 15 animals each. Group A was treated as control, Group B and Group C received 45 mg/kg STZ once at the start of the experiment whereas Group C additionally received 600 mg/kg Vitamin E Intramuscularly 3 times weekly. Serum glucose and Creatinine concentrations were measured at the beginning of the experiment and once weekly. Serum glucose and Creatinine levels were significantly elevated in Group B as compared to control. In Group C, blood glucose was elevated but the levels of serum Creatinine were significantly reduced, when compared to group B. our findings conclude that Vitamin E supplementation may have protective effects against deterioration of renal function brought about by free radical toxicity in diabetes mellitus

Microalbuminuria como elemento de predicción de nefropatía y riesgo cardiovascular en pacientes diabéticos / Microalbuminuria as predictor of nephropathy and cardiovascular risk factor among diabetic patients

Microalbuminuria, defined as urinary excretion of albumin in the range of 30-300 mg/g creatinine, affects 20-30 percent of the type 2 diabetic (DM2) patients and 30-40 percent of type 1 diabetic (DM1) patients who, without intervention, progress to macroalbuminuria at rates of 5 and 7.5 percent per year, respectively. Hyperglycemia, by activating different metabolic pathways and the renin-angiotensin-aldosterone system, determines an increase in reactive oxygen species (ROS) which finally causes endothelial dysfunction. Albuminuria reflects a generalized endothelial dysfunction, that is related to cardiovascular disease in diabetic patients. Therefore, microalbuminuria becomes a predictor of renal damage, a coronary risk factor and a predictor of cardiovascular diseases. Several studies have demonstrated that progression of albuminuria can be prevented in normotensive and hypertensive DM1 and DM2 patients with the use of an inhibitor of angiotensin converting enzyme II or an antagonist of the angiotensin II receptor. These measures also provide cardiovascular protection in diabetic patients, an effect that is independent of the hypotensive action of the drug. In microalbuminuric diabetic patients, treatment should be oriented to diminish or avoid progression of microalbuminuria, and to maintain blood pressure, glucose and lipids within the recommended limits to avoid vascular and renal damage.

Enfermedad renal en la diabetes: a propósito del día mundial del riñón: [editorial] / Diabetic renal disease: the World Kidney Day in Chile: [editorial]

The third version of the World Kidney Day will be held on May 13, 2010 in Chile and will be focused in diabetic renal damage, the main cause of chronic kidney disease (CKD). Currently, we are living a pandemia of CKD, a progressive and irreversible condition with high social and economic impact. In Chile, we have 857 patients per million inhabitants in hemodialysis and 35 percent are secondary to diabetes. Our general prevalence of diabetes is 4.2 percent, rising to 15 percent in people aged more than 64 years. With a 34 percent prevalence of hypertension, an aging population, high prevalence of obesity, and a sedentary lifestyle, there is an estimation of a rise in 85 percent of the prevalence of diabetes in South-America, for the next decades. The steps to be taken are clear: campaigns should be aimed at (1) prevention of type 2 diabetes; (2) screening for early diabetic kidney disease; (3) increasing patient awareness of kidney disease; (4) using medications of proven strategy and fnally (5) research on new therapies. These concepts must be included in community and professional education to reduce the effects of this pandemia.

Aldose Reductase Inhibitor Ameliorates Renal Vascular Endothelial Growth Factor Expression in Streptozotocin-Induced Diabetic Rats

PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg.kg(-1).day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg.kg(-1).day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.

Effect of allopurinol in decreasing proteinuria in type 2 diabetic patients

Diabetic nephropathy is the most prevalent cause of end-stage renal disease. Besides factors such as angiotensin II, cytokines, and vascular endothelial growth factor, uric acid may play a role as the underlying cause of diabetic nephropathy. We evaluated allopurinol effects on proteinuria in diabetic patients with nephropathy. In a double-blinded randomized controlled trial on 40 patients with type 2 diabetes mellitus and diabetic nephropathy [proteinuria, at least 500 mg/24 h and a serum creatinine level less than 3 mg/dL], allopurinol [100 mg/d] was compared with placebo. Administration of antihypertensive and renoprotective drugs [angiotensin-converting enzyme inhibitors and angiotensin receptor blockers continued for both groups, without changes in dosage. Proteinuria was compared at baseline and 2 and 4 months between the two groups. Each group consisted of 9 men and 11 women. There were no difference between two groups regarding age, body mass index, duration of diabetes mellitus, systolic and diastolic blood pressure, fasting blood glucose, blood urea nitrogen, serum creatinine, serum potassium, and urine volume. Serum levels of uric acid [P=.02] and 24-hour urine protein [P=.049] were significantly lower in the patients on allopurinol, after 4 months of receiving allopurinol, compared with the control group. Low-dose allopurinol can reduce severity of proteinuria after 4 months of drug administration, which is probably due to decreasing the serum level of uric acid. Thus, allopurinol can be administered as an adjuvant cost-effective therapy for patients with diabetic nephropathy

Long-Term Effects of Rosiglitazone on the Progressive Decline in Renal Function in Patients With Type 2 Diabetes

BACKGROUND/AIMS: Thiazolidinediones reduce urinary albumin excretion and may prevent the development of renal injury. We evaluated the long-term effects of rosiglitazone on the progression of renal dysfunction in patients with type 2 diabetes mellitus. METHODS: We enrolled patients with type 2 diabetes mellitus who initially had normal or mildly impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of 60-120 mL/min per 1.73 m2, and normoalbuminuria. Patients were divided into two groups according to their use of rosiglitazone during 3 years of follow-up: those treated with rosiglitazone (rosiglitazone group, n=52) and those treated without rosiglitazone (control group, n=85). Progression of renal dysfunction was defined as a decrease in eGFR of > or =9 mL/min per 1.73 m2 after 3 years. RESULTS: A greater difference was observed in the decrease in eGFR between the rosiglitazone and control groups after 3 years (3.8+/-9.9 vs. 12.6+/-10.5 mL/min per 1.73 m2, p<0.001). Seventeen of 52 (32.7%) patients in the rosiglitazone group and 53 of 85 (62.3%) patients in the control group showed progression of renal dysfunction (p=0.001). The progressors had a longer duration of diabetes (6.7+/-5.9 vs. 3.9+/-4.1 years, p=0.002), higher HbA1c levels (7.4+/-1.8 vs. 6.8+/-1.3%, p=0.023), and less frequent use of rosiglitazone (24.2 vs. 52.2%, p<0.001) compared to non-progressors. Multiple logistic regression analysis revealed that the use of rosiglitazone was a significant and independent predictor of the progression of renal dysfunction. CONCLUSIONS: This study suggests that rosiglitazone theatment slows the progressive deterioration of renal function in patients with type 2 diabetes.

Experimental diabetic nephropathy can be prevented by propolis: effect on metabolic disturbances and renal oxidative parameters

Oxidative stress may play a key role in the pathogenesis of diabetic nephropathy. Propolis and its extract have antioxidant properties. The effect of ethanolic extract of propolis against experimental diabetes mellitus-associated changes was examined. Diabetes was induced experimentally in rats by i.p. injection of streptozotocin [STZ] in a dose of 60 mg/kg bwt for 3 successive days. Blood urea nitrogen [BNU], creatinine, glucose, lipid profile, malondialdehyde [MDA] and urinary albumin were measured. Superoxide dimutase [SOD], glutathione [GSH], catalase [CAT] and MDA were measured in the renal tissue. The results showed decreased body weight and increased kidney weight in diabetic animals. Compared to the control normal rats, diabetic rats had higher blood glucose, BNU, creatinine, total cholesterol, triglycerides, low-density lipoprotein-cholesterol [LDL-C], MDA and urinary albumin and lower high-density lipoprotein-cholesterol [HDL-C] levels. Moreover, renal tissue MDA was markedly increased while SOD, GSH and CAT were significantly decreased. Oral administration of propolis extract in doses of 100,200 and 300 mg/kg bwt improved the body and kidney weights, serum glucose, lipid profile, MDA and renal function tests. Renal GSH, SOD and CAT were significantly increased while MDA was markedly reduced. These results may suggest a strong antioxidant effect of propolis which can ameliorate oxidative stress and delay the occurrence of diabetic nephropathy in diabetes mellitus

Chronic renal failure; association of diabetes mellitus

To find the effect of diabetes mellitus on the development of Chronic renal failure [CRF]. Descriptive Cross-sectional study. Allied Hospital, Faisalabad. From May 2008 to June 2008. Forty-Five patients of CRF were selected for study by convenient method technique from admitted patients in dialysis unit of Allied Hospital Faisalabad. In our study, out of 45 patients of CRF, 25 [55.6%] were found to be diabetic. The effect of diabetes on the development CRF was highest in age group of 71-85 years that was 100%. In this study diabetes mellitus was found to be more prevalent among married CRF patients [62%] as compared to unmarried patients among whom it was [17%]. Among the male CRF patients 54% were diabetic, while among the female CRF patients 57% were diabetic. Percentage of CAF patients having diabetes mellitus was 55.6%. From the above results it is concluded that effect of diabetes mellitus on the development of CRF increases with age. Diabetes mellitus was found to be more prevalent among female CRF patients and also among the married CRF patients. The development of Chronic renal failure can be prevented by early diagnosis and treatment of diabetes mellitus