Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy is a serious complication of diabetes associated with a poor prognosis which deteriorates to end-stage renal disease. Increased urinary excretion of protein and albumin are early clinical markers for diabetic renal disease and increased risk of cardiovascular disease. Diabetes causes activation of the renal endothelin system inducing renal damage. We analyzed the effects of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on diabetes-induced alterations of kidney function and morphology in rats with streptozotocin-induced diabetes. The effects of SLV306 (30 mg/kg per day), captopril (10 mg/kg per day), and placebo on urinary protein and albumin excretion as well as on blood pressure were studied in diabetic rats in comparison to non-diabetic control rats. The rats were treated for 20 weeks. At the end of the study kidney morphology was also analyzed using computer-aided image analysis systems. Serum glucose and blood pressure were similar in all diabetic groups. No side-effects were observed with SLV306 and captopril treatment. Protein excretion was 17.3 +/- 3.0 mg/24 hours in untreated diabetic rats. Protein excretion decreased significantly in the SLV306 (4.8 +/- 0.9 mg/24 hours; P = 0.03 vs untreated diabetic rats) as well as in the captopril (5.1 +/- 1.0 mg/24 hours; P = 0.03 vs untreated diabetic rats) -treated diabetic rats. Albumin excretion was 0.51 +/- 0.12 mg/24 hours in the untreated diabetic group and decreased likewise in the SLV306-treated diabetic rats (0.09 +/- 0.03 mg/24 hours; P = 0.04 vs untreated diabetic rats). The captopril-treated diabetic rats showed a strong trend towards reduced albumin excretion (0.12 +/- 0.04 mg/24 hours; P = 0.06 vs untreated diabetic rats). Computer-aided image analysis revealed that renal interstitial matrix content was significantly decreased in diabetic rats treated with either the angiotensin-converting enzyme inhibitor or the neutral endopeptidase/endothelin-converting enzyme inhibitor as compared to untreated diabetic rats. It was found that SLV306 decreases renal matrix protein content as well as protein and albumin excretion in diabetic rats independent of blood pressure. These effects are comparable to those of angiotensinconverting enzyme inhibition.
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PMID:Inhibition of both neutral endopeptidase and endothelin-converting enzyme by SLV306 reduces proteinuria and urinary albumin excretion in diabetic rats. 1583 65

We aimed to investigate the effects of Liuwei Dihuang decoction (LW) on the endothelin-1-reactive oxidative species (ET-ROS) system and matrix metalloproteinases (MMPs) in the early diabetic nephropathy induced by streptozotocin (STZ) in rats. Rats were divided into six groups as follows: the control group, the untreated model group, the treated groups with the LW (5, 10 and 15 g kg(-1), p.o.) and the aminoguanidine-treated group (100 mg kg(-1), orally). The treatment was performed for 4 weeks, beginning on the fifth week after one intraperitoneal injection of STZ (65 mg kg(-1)). In the untreated model group, increased blood glucose, decreased plasma insulin level and an impaired renal function were observed. There was an altered redox system shown by an increased malondialdehyde and decreased activity of glutathione peroxidase and superoxide dismutase in the renal cortex. An enhanced inducible nitric oxide synthetase, total nitric oxide synthase and constitutive nitric oxide synthase and a declined nitric oxide were found. An increased extracellular matrix was indicated by an abnormality of MMP-2 and MMP-9 activities and an increase in hydroxyproline. An up-regulated ET-1 level and increased mRNA expression of endothelin-converting enzyme, preproET-1 and ET( A) receptor were presented in the affected renal cortex, but no change in ET(B) receptor mRNA. The LW was most effective in reversing these changes in diabetic rats and was as effective as aminoguanidine. The benefits of the extracts in relieving the abnormalities in early diabetic nephropathy are likely to be mediated by suppression of the renal ET-ROS system and escalating the activity of MMPs.
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PMID:Protective effect of Liuwei Dihuang decoction on early diabetic nephropathy induced by streptozotocin via modulating ET-ROS axis and matrix metalloproteinase activity in rats. 1940 9