Top

BMC Nephrology

Published in:

Open Access 01-12-2017 | Research article

Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression

Authors: Lingyu Xue, Xiaoqing Feng, Chuanhai Wang, Xuebin Zhang, Wenqiang Sun, Kebo Yu

Published in: BMC Nephrology | Issue 1/2017

Abstract

Background

This study aimed to investigate the effects of benazepril hydrochloride (BH) on proteinuria and ANGPTL-4 expression in a diabetic nephropathy (DN) rat model.

Methods

A total of 72 Wistar male rats were randomly divided into three groups: normal control (NC), DN group and BH treatment (BH) groups. The DN model was induced by streptozotocin (STZ). Weight, glucose, proteinuria, biochemical indicators and the kidney weight index were examined at 8, 12 and 16 weeks. In addition, ANGPTL-4 protein and mRNA expressions were assessed by immunohistochemistry and qRT-PCR, respectively. Relationships between ANGPTL-4 and biochemical indicators were investigated using Spearman analysis.

Results

Weight was significantly lower but glucose levels were significantly higher in both the DN and BH groups than in the NC group (P < 0.05). Compared with the DN group, proteinuria, urea, creatinine, triglycerides and total cholesterol levels were decreased, whereas the albumin level was increased after BH treatment (all P < 0.05). Furthermore, BH diminished kidney volume and ameliorated the pathological changes associated with DN. ANGPTL-4 expression was significantly decreased after BH treatment, and ANGPTL-4 expression was highly correlated with biochemical indicators of DN (P < 0.05).

Conclusions

Benazepril hydrochloride improves DN and decreases proteinuria by decreasing ANGPTL-4 expression.

Matsui T, Yamagishi S, Takeuchi M, Ueda S, Fukami K, Okuda S. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation. Biochem Biophys Res Commun. 2010;398(2):326–30.CrossRefPubMed

Kong LL, Wu H, Cui WP, Zhou WH, Luo P, Sun J, Yuan H, Miao LN. Advances in murine models of diabetic nephropathy. J Diabetes Res. 2013;2013:797548.CrossRefPubMedPubMedCentral

Keane WF, Brenner BM, De Zeeuw D, Grunfeld J-P, Mcgill J, Mitch WE, Ribeiro AB, Shahinfar S, Simpson RL, Snapinn SM. The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int. 2003;63(4):1499–507.CrossRefPubMed

Dronavalli S, Duka I, Bakris GL. The pathogenesis of diabetic nephropathy. Nat Clin Pract Endocrinol Metab. 2008;4(8):444–52.CrossRefPubMed

Yamamoto Y, Maeshima Y, Kitayama H, Kitamura S, Takazawa Y, Sugiyama H, Yamasaki Y, Makino H. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy. Diabetes. 2004;53(7):1831–40.CrossRefPubMed

Salchell S, Mathieson PW. Angiopoietins: microvascular modulators with potential roles in glomerular pathophysiology. J Nephrol. 2003;16(2):168–78.

Lai KN, Leung JC, Tang SC. The renin-angiotensin system. Contrib Nephrol. 2011;170:135–44.CrossRefPubMed

Clement LC, Avila-Casado C, Mace C, Soria E, Bakker WW, Kersten S, Chugh SS. Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med. 2011;17(1):117–22.CrossRefPubMed

Reiser J. Filtering new facts about kidney disease. Nat Med. 2011;17(1):44–5.CrossRefPubMed

10.

Chugh SS, Clement LC, Macé C. New insights into human minimal change disease: lessons from animal models. Am J Kidney Dis. 2012;59(2):284–92.CrossRefPubMed

11.

Liu X, Liu L, Chen P, Zhou L, Zhang Y, Wu Y, Jiang L, Cheng D, Huang W, Yi D. Clinical trials of traditional Chinese medicine in the treatment of diabetic nephropathy—A systematic review based on a subgroup analysis. J Ethnopharmacol. 2014;151(2):810–9.CrossRefPubMed

12.

Cooper ME. Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy. Diabetologia. 2001;44(11):1957–72.CrossRefPubMed

13.

Allard J, Buleon M, Cellier E, Renaud I, Pecher C, Praddaude F, Conti M, Tack I, Girolami JP. ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats. Am J Physiol Renal Physiol. 2007;293(4):F1083–92.CrossRefPubMed

14.

Naguib IA, Abdelaleem EA, Draz ME, Zaazaa HE. Linear support vector regression and partial least squares chemometric models for determination of Hydrochlorothiazide and Benazepril hydrochloride in presence of related impurities: a comparative study. Spectrochim Acta A Mol Biomol Spectrosc. 2014;130:350–6.CrossRefPubMed

15.

Brittain HG. Profiles of Drug Substances, Excipients, and Related Methodology. Analy Profiles Drug Subst Excipients. 2002;29:1–5.CrossRef

16.

Gismondi RA, Oigman W, Bedirian R, Pozzobon CR, Ladeira MC, Neves MF. Comparison of benazepril and losartan on endothelial function and vascular stiffness in patients with Type 2 diabetes mellitus and hypertension: A randomized controlled trial. JRAAS. 2015;16:967.PubMed

17.

Zhi-hui B, Zhen M. Combination Therapy of Benazepril Hydrochloride with Hydrochlor-othiazide for Renal Hypertension. Guide China Med. 2012;34:321.

18.

Wang W, Li L, Zhou Z, Gao J, Sun Y. Effect of spironolactone combined with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers on chronic glomerular disease. Exp Ther Med. 2013;6(6):1527–31.CrossRefPubMedPubMedCentral

19.

Clement LC, Mace C, Avila-Casado C, Joles JA, Kersten S, Chugh SS. Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome. Nat Med. 2014;20(1):37–46.CrossRefPubMed

20.

Chugh SS, Mace C, Clement LC, Del Nogal AM, Marshall CB. Angiopoietin-like 4 based therapeutics for proteinuria and kidney disease. Front Pharmacol. 2014;5:23.CrossRefPubMedPubMedCentral

21.

Peng L, Ma J, Cui R, Chen X, Wei SY, Wei QJ, Li B. The calcineurin inhibitor tacrolimus reduces proteinuria in membranous nephropathy accompanied by a decrease in angiopoietin-like-4. PLoS One. 2014;9(8):e106164.CrossRefPubMedPubMedCentral

22.

Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC. TGF-beta signal transduction and mesangial cell fibrogenesis. Am J Physiol Renal Physiol. 2003;284(2):F243–52.CrossRefPubMed

23.

Flyvbjerg A. Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease. Diabetologia. 2000;43(10):1205–23.CrossRefPubMed

24.

Quintero P, González-Muniesa P, Garcia-Diaz DF, Martínez JA. Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3-L1 adipocytes. J Physiol Biochem. 2012;68(4):663–9.CrossRefPubMed

25.

Oike Y, Tabata M. Angiopoietin-Like Proteins Potential Therapeutic Targets for Metabolic Syndrome and Cardiovascular Disease. Circ J. 2009;73(12):2192–7.CrossRefPubMed

26.

Musial DC, da Silva Júnior ED, da Silva RM, Miranda-Ferreira R, Lima-Landman MTR, Jurkiewicz A, García AG, Jurkiewicz NH. Increase of angiotensin-converting enzyme activity and peripheral sympathetic dysfunction could contribute to hypertension development in streptozotocin-induced diabetic rats. Diab Vasc Dis Res. 2013;10:498. 1479164113496441CrossRefPubMed

Title: Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression
Authors: Lingyu Xue
Xiaoqing Feng
Chuanhai Wang
Xuebin Zhang
Wenqiang Sun
Kebo Yu
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Nephrology / Issue 1/2017
Electronic ISSN: 1471-2369
DOI: https://doi.org/10.1186/s12882-017-0724-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Association of estimated glomerular filtration rate and urine albumin-to-creatinine ratio with incidence of cardiovascular diseases and mortality in chinese patients with type 2 diabetes mellitus – a population-based retrospective cohort study

Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients

Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings

Unusual clinical outcome of primary Hyperoxaluria type 1 in Tunisian patients carrying 33_34InsC mutation

MDRD vs. CKD-EPI in comparison to 51Chromium EDTA: a cross sectional study of Malaysian CKD cohort

How does pre-dialysis education need to change? Findings from a qualitative study with staff and patients

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page