Calcium Dobesilate Prevents Diabetic Kidney Disease by Decreasing Bim and Inhibiting Apoptosis of Renal Proximal Tubular Epithelial Cells.

Apoptosis of renal proximal tubular epithelial cells (PTECs) plays a vital role in the pathogenesis and progression of diabetic kidney disease (DKD). Calcium dobesilate is a vascular protective compound used for treatment of diabetic retinopathy and chronic venous insufficiency. The aim of this study was to determine whether calcium dobesilate can protect PTECs from glucose-induced apoptosis and the potential mechanism of this effect. It is indicated that high glucose promoted abnormal apoptosis of HK2 cells, which was inhibited by treatment of calcium dobesilate, while Bim expression decreased in response to calcium dobesilate in high-glucose-treated HK2 cells. These findings confirmed the therapeutic effects of calcium dobesilate on DKD and emphasized the importance of it as a potentially crucial drug in treatment of DKD.

[1]  Lin Deng,et al.  HCV upregulates Bim through the ROS/JNK signalling pathway, leading to Bax-mediated apoptosis. , 2015, The Journal of general virology.

[2]  A. Gvritishvili,et al.  Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF) Peptide Prevents the Progression of Diabetic Renal Injury , 2015, PloS one.

[3]  K. Alitalo,et al.  Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-β , 2014, Proceedings of the National Academy of Sciences.

[4]  U. Linnenkamp,et al.  Global estimates of diabetes prevalence for 2013 and projections for 2035. , 2014, Diabetes research and clinical practice.

[5]  J. Williamson,et al.  Albuminuria and cognitive decline in people with diabetes and normal renal function. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[6]  G. Zheng,et al.  [Evaluation of calcium dobesilate for its anti-cataract potential in experimental rat models]. , 2013, [Zhonghua yan ke za zhi] Chinese journal of ophthalmology.

[7]  Xiaoqian Zhang Therapeutic effects of calcium dobesilate on diabetic nephropathy mediated through reduction of expression of PAI-1 , 2012, Experimental and therapeutic medicine.

[8]  J. Bonventre Can we target tubular damage to prevent renal function decline in diabetes? , 2012, Seminars in nephrology.

[9]  C. Draman,et al.  A retrospective review of diabetic nephropathy patients during referral to the sub-urban nephrology clinic. , 2012, Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia.

[10]  S. Tang,et al.  The pathogenic role of the renal proximal tubular cell in diabetic nephropathy. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  Akihiro Tojo,et al.  Mechanisms of Glomerular Albumin Filtration and Tubular Reabsorption , 2012, International journal of nephrology.

[12]  E. Abdel-Rahman,et al.  Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches , 2012, Journal of General Internal Medicine.

[13]  V. Vallon The proximal tubule in the pathophysiology of the diabetic kidney. , 2011, American journal of physiology. Regulatory, integrative and comparative physiology.

[14]  D. Williamson,et al.  Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence , 2010, Population health metrics.

[15]  H. Soncul,et al.  Effects of calcium dobesilate and diosmin-hesperidin on apoptosis of venous wall in primary varicose veins. , 2008, VASA. Zeitschrift fur Gefasskrankheiten.

[16]  J. Cunha-Vaz,et al.  Effect of calcium dobesilate on progression of early diabetic retinopathy: a randomised double-blind study , 2006, Graefe's Archive for Clinical and Experimental Ophthalmology.

[17]  T. Kuwana,et al.  BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. , 2005, Molecular cell.

[18]  Maristela L Onozato,et al.  Reduced albumin reabsorption in the proximal tubule of early-stage diabetic rats , 2001, Histochemistry and Cell Biology.

[19]  Soo-Hyun Park,et al.  High glucose inhibits renal proximal tubule cell proliferation and involves PKC, oxidative stress, and TGF-beta 1. , 2001, Kidney international.

[20]  C. Print,et al.  The proapoptotic BH3-only protein bim is expressed in hematopoietic, epithelial, neuronal, and germ cells. , 2000, The American journal of pathology.

[21]  C. Mogensen,et al.  Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas , 1999, Diabetologia.

[22]  A. Strasser,et al.  Bim: a novel member of the Bcl‐2 family that promotes apoptosis , 1998, The EMBO journal.

[23]  R. Meadows,et al.  X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death , 1996, Nature.

[24]  P. E. Nagao,et al.  Reactive oxygen species involved in apoptosis induction of human respiratory epithelial (A549) cells by Streptococcus agalactiae. , 2016, Microbiology.

[25]  G. Deferrari,et al.  Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells. , 2004, Journal of the American Society of Nephrology : JASN.

[26]  H. Allain,et al.  Safety of Calcium Dobesilate in Chronic Venous Disease, Diabetic Retinopathy and Haemorrhoids , 2004, Drug safety.