Enhanced Effect of Combined Treatment with SMP-534 (Antifibrotic Agent) and Losartan in Diabetic Nephropathy

2006 ◽  
Vol 26 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Eiji Sugaru ◽  
Tsutomu Nakagawa ◽  
Michiko Ono-Kishino ◽  
Jun Nagamine ◽  
Teruhisa Tokunaga ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Combined Treatment

scholarly journals Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

scholarly journals Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy

Renal Failure ◽  
2015 ◽  
Vol 37 (4) ◽  
pp. 548-561 ◽  
Author(s):  
Feifeng Ren ◽  
Lin Tang ◽  
Yin Cai ◽  
Xin Yuan ◽  
Wenhan Huang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Efficacy And Safety

scholarly journals Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xia Zou ◽  
Xiao-xi Zhang ◽  
Xin-yu Liu ◽  
Rong Li ◽  
Min Wang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Combined Treatment ◽  
Renin Angiotensin System ◽  
Functional Impairments ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renal Kallikrein ◽  
Dual Blockade

Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN).Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF-)βandα-smooth muscle action (SMA).Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (allP<0.05). Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, andα-SMA.Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

scholarly journals Efficacy of tripterygium glycosides combined with ARB on diabetic nephropathy: a meta-analysis

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Xue Wu ◽  
Youye Huang ◽  
Yao Zhang ◽  
Chunling He ◽  
Yongli Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Mean Difference ◽  
Biomedical Literature ◽  
Controlled Trials ◽  
Angiotensin Ii Receptor Blocker ◽  
Cochrane Central Register ◽  
Significant Difference ◽  
Tripterygium Glycosides

Abstract The purpose of this meta-analysis was to evaluate the beneficial and adverse effects of tripterygium glycosides (TGs) combined with angiotensin II receptor blocker (ARB) on diabetic nephropathy (DN). We searched for randomized controlled trials (RCTs) in PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Biomedical Literature Database, China Science and Technology Journal Database up to June 2017. Weighted mean difference (WMD) and standardized mean difference (SMD) were used for continuous variables and all variables were expressed by 95% confidence interval (CI). Twenty-three studies with 1810 DN patients were included in this meta-analysis. TG combined with ARB statistically significantly improved 24-h urinary total protein (24-h UTP) (SMD = −1.46; 95% CI = −1.84 to −1.09; P&lt;0.00001), urinary albumin excretion rate (UAER) (SMD = −6.9; 95% CI = −9.65 to −4.14, P&lt;0.00001), serum creatinine (SCr) (WMD = −7.65.14; 95% CI = −12.99 to −2.31; P=0.005) and albumin (Alb) (WMD = 5.7; 95% CI = 4.44 to 6.96; P&lt;0.00001) more than did ARB alone. TG combined with ARB statistically significantly affected the level of serum glutamic pyruvic transaminase (SGPT) (WMD = 1.08; 95% CI = 0.04 to 2.12, P=0.04) more than did ARB alone. Compared with ARB alone, TG combined with ARB showed no significant difference in improving blood urea nitrogen (BUN) and hemoglobin A1c (HbA1c). Minor side effects from the combined treatment were observed and mainly focused on the abnormal liver function. TG combined with ARB offers a novel concept in treating DN, more high-quality RCTs are needed for better understanding and applying the combined treatment in DN.

scholarly journals Combined losartan and nitro-oleic acid remarkably improves diabetic nephropathy in mice

2013 ◽  
Vol 305 (11) ◽  
pp. F1555-F1562 ◽  
Author(s):  
Ying Liu ◽  
Zhanjun Jia ◽  
Shanshan Liu ◽  
Maicy Downton ◽  
Gang Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Oleic Acid ◽  
Renal Disease ◽  
Therapeutic Potential ◽  
Combined Treatment ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Filtration Barrier ◽  
Stage Renal Disease

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). The inhibitors of renin-angiotensin-aldosterone system (RAAS) can alleviate some of the symptoms of DN but fail to stop the progression to ESRD. Our previous studies demonstrate renoprotective action of nitro-oleic acid (OA-NO2) in several rodent models of renal disease. Here we examined the therapeutic potential and the underlying mechanism of combination of losartan and OA-NO2 in db/db mice. OA-NO2 was infused at 5 mg·kg−1·day−1 via osmotic minipump, and losartan was incorporated into diet at 10 mg·kg−1·day−1, each administered alone or in combination for 2 wk. Diabetic db/db mice developed progressive albuminuria and glomerulosclerosis, accompanied by podocytes loss, increased indexes of renal fibrosis, oxidative stress, and inflammation. Treatment of the diabetic mice with OA-NO2 or losartan alone moderately ameliorated kidney injury; however, the combined treatment remarkably reduced albuminuria, restored glomerular filtration barrier structure, and attenuated glomerulosclerosis, accompanied with significant suppression of renal oxidative stress and inflammation. These data demonstrate that combination of losartan and OA-NO2 effectively reverses renal injury in DN.

scholarly journals Supplementation of Abelmoschus manihot Ameliorates Diabetic Nephropathy and Hepatic Steatosis by Activating Autophagy in Mice

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1703 ◽  
Author(s):  
Hwajin Kim ◽  
Theodomir Dusabimana ◽  
So Kim ◽  
Jihyun Je ◽  
Kyuho Jeong ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mitochondrial Dynamics ◽  
Periodic Acid ◽  
Combined Treatment ◽  
Fasting Blood Glucose ◽  
Diabetic Complication ◽  
Protective Mechanism ◽  
Protein Accumulation ◽  
Leaf Extracts ◽  
Periodic Acid Schiff

Diabetic nephropathy (DN) is a diabetic complication marked by albuminuria and a decline of the glomerular filtration rate. Diabetic kidneys are defective in the autophagy process and mitochondrial function and their enhancement of activity alleviates the pathology. In this paper, we developed a mouse model of DN by a combined treatment of a high-fat diet and streptozotocin after unilateral nephrectomy and supplementation with flower or leaf extracts of Abelmoschus manihot (AM) were tested. The preventive effects of the extracts on DN pathology and changes on autophagy and mitochondrial proteins were investigated. DN mice showed a significant increase in fasting blood glucose, plasma creatinine, blood urea nitrogen, and urinary albumin levels. Periodic acid–Schiff and Sirius red staining of the diabetic kidney presented a significant change in glomerular and tubular structures that was associated with podocyte loss and fibrotic protein accumulation. These changes were attenuated by AM extract treatment in DN mice. In addition, hepatic injury, proinflammatory cytokines, and lipid accumulation were decreased by AM extracts in DN mice. As a protective mechanism, AM extracts significantly increased the expression of proteins by regulating autophagy and mitochondrial dynamics, which potentially prevented the kidney and liver from accumulating pathogenic proteins and dysfunctional mitochondria, which alleviated the progression of DN.

scholarly journals Nephroprotective Effect of Coenzyme Q10 alone and in Combination with N-acetylcysteine in Diabetic Nephropathy

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
S. Mahajan Manojkumar ◽  
B. Upaganlawar Aman ◽  
D. Upasani Chandrashekar
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Coenzyme Q10 ◽  
Tissue Damage ◽  
Microvascular Complications ◽  
Combined Treatment ◽  
Diabetic Rats ◽  
Renal Physiology ◽  
Chronic Hyperglycaemia ◽  
Nephroprotective Effect

Abstract Aim Oxidative stress due to chronic hyperglycaemia is a key factor in the development and progression of various microvascular complications including diabetic nephropathy (DN) and associated renal injury. Treatment with antioxidants is one of the strategies to protect the kidney from oxidative tissue damage to improve renal physiology during DN. The investigation, therefore, was designed to assess the nephroprotective effect of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), either alone or in combination in streptozotocin (STZ)-nicotinamide (NAD) induced diabetic nephropathy (DN) in rats. Methods T2DM induced by STZ (55 mg/kg, i.p.)-NAD (110 mg/kg, i.p.) in Sprague-Dawley rats (220–250 g) was confirmed by the elevated blood glucose level and glycated haemoglobin. DN was assessed by renal function tests. The diabetic rats were treated with CoQ10 (10 mg/kg, p.o.) and/or NAC (300 mg/kg, p.o.) for 8 weeks after confirmation of DN. Oxidative tissue damage due to STZ-NAD was estimated by malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH), myeloperoxidase (MPO) and nitric oxide (NO) in the renal homogenate. Results Data showed significant alteration in serum and urinary creatinine, total protein, albumin, serum urea, blood urea nitrogen (BUN) and uric acid in diabetic animals as compared to the control rats. CoQ10 and/or NAC effectively alleviated the disturbances in renal function. Diabetic rats showed increased MDA, decreased SOD and CAT activities and decreased GSH along with a significant increase in MPO activity and nitrite content. Treatment with the aforementioned antioxidants and their combination ameliorated the kidney damage as indicated by the reduced OS with improved renal function. Conclusion The investigation suggests that the chronic hyperglycaemia-induced OS leads to the development and progression of DN. The combined treatment with CoQ10 and NAC has shown a remarkable nephroprotective effect suggesting that combined antioxidant therapy with CoQ10 and NAC may be useful in the attenuation of DN.

Amelioration of Established Diabetic Nephropathy by Combined Treatment with SMP-534 (Antifibrotic Agent) and Losartan in db/db Mice

2006 ◽  
Vol 105 (2) ◽  
pp. e45-e52 ◽  
Author(s):  
Eiji Sugaru ◽  
Tsutomu Nakagawa ◽  
Michiko Ono-Kishino ◽  
Jun Nagamine ◽  
Teruhisa Tokunaga ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Combined Treatment

Unlike each drug alone, lisinopril if combined with avosentan promotes regression of renal lesions in experimental diabetes

2009 ◽  
Vol 297 (5) ◽  
pp. F1448-F1456 ◽  
Author(s):  
Elena Gagliardini ◽  
Daniela Corna ◽  
Carla Zoja ◽  
Fabio Sangalli ◽  
Fabiola Carrara ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Receptor Antagonist ◽  
Ace Inhibitor ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Diabetic Rats ◽  
Size Selectivity ◽  
Glomerular Lesions ◽  
Glomerular Size ◽  
And Function

In the present study, we evaluated the effect of simultaneously blocking angiotensin II synthesis and endothelin (ET)-1 activity as a multimodal intervention to implement renoprotection in overt diabetic nephropathy. Mechanisms underlying combined therapy effectiveness were addressed by investigating podocyte structure and function and glomerular barrier size-selective properties. Uninephrectomized rats made diabetic by streptozotocin received orally placebo, lisinopril (12.5 mg/l), the ETA receptor antagonist avosentan (30 mg/kg), or their combination from 4 (when animals had proteinuria) to 8 mo. Proteinuria, renal damage, podocyte number, nephrin expression, and glomerular size selectivity by graded-size Ficoll molecule fractional clearance were assessed. Combined therapy normalized proteinuria, provided complete protection from tubulointerstitial damage, and induced regression of glomerular lesions, while only a partial renoprotection was achieved by each drug alone. Lisinopril plus avosentan restored to normal values the number of podocytes. Single therapies only limited podocyte depletion. Defective nephrin expression of diabetes was prevented by each drug. Altered glomerular size selectivity to large macromolecules of diabetic rats was remarkably improved by lisinopril and the combined treatment. Avosentan ameliorated peritubular capillary architecture and reduced interstitial inflammation and fibrosis. The ACE inhibitor and ETA receptor antagonist induced regression of glomerular lesions in overt diabetic nephropathy. Regression of renal disease was conceivably the result of the synergistic effect of the ACE inhibitor of preserving glomerular permselective properties and the ETA antagonist in improving tubulointerstitial changes. These findings provide mechanistic insights to explain the antiproteinuric effect of this combined therapy in diabetes.

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