DF-5 compound delays development of diabetic nephropathy in rats

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Advanced glycation end-products play an important role in the development of diabetic complications, so slowing down of glycated proteins’ cross-links formation have been suggested as a potential therapeutic option for the treatment of vascular diabetic complications and preventing their progression.

The aim of the work was to assess the influence of novel anticrosslinking agent DF-5 on the renal advanced glycation end-products and collagen contents, body weight, blood glucose and glycated hemoglobin levels and the development of early renal disease in streptozotocin-induced diabetic rats.

Materials and methods. 40 male Sprague-Dawley rats were used in the study. Two months after inducing diabetes, the study substance was administered intragastrically once a day for 28 days (12.5 mg/kg). Measurements included the assessment of blood glucose and HbA1c levels, the evaluation of the renal function, and the results of histology and immunohistochemical staining of kidneys.

Results. A repeated intragastric administration of DF-5 for 30 days significantly reduced the level of HbA1c in the blood, but did not affect the level of fasting blood glucose. DF-5 compound significantly reduced proteinuria and prevented kidney damage in experimental animals by limiting damage of the glomeruli and tubules. It was found that DF-5 inhibits the progression of an early renal dysfunction in rats with streptozotocin-induced diabetic nephropathy. This was associated with a decreased accumulation of advanced glycation end-products in the kidney, accompanied by the improvement of both renal morphology and function.

Conclusion. The results obtained provide investigators with additional therapeutic options for the treatment of diabetic nephropathy and possibly other complications of diabetes.

作者简介

Alexander Spasov

Volgograd State Medical University; Volgograd Medical Research Center

Email: aspasov@mail.ru
ORCID iD: 0000-0002-7185-4826

Doctor of Sciences (Medicine), Academician of RAS, Head of the Pharmacology and Bioinformatics Department, Volgograd State Medical University; Head of the Laboratory of Experimental Pharmacology, Volgograd Medical Research Center

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 1, Pavshikh Bortsov Sq., Volgograd, 400131

Olga Zhukovskaya

Institute of Physical and Organic Chemistry, Southern Federal University

Email: zhukowskaia.ol@yandex.ru
ORCID iD: 0000-0003-2485-2139

Candidate of Sciences (Chemistry), Senior researcher of the Organic Synthesis Laboratory

俄罗斯联邦, Bldg 2, 194, Stachki Ave., Rostov-on-Don, 344090

Andrey Rashchenko

Volgograd State Medical University

Email: a.rashencko@yandex.ru

Candidate of Sciences (Pharmacy), Senior researcher of the Metabotropic Drugs Laboratory

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131

Anasthasia Brigadirova

Volgograd State Medical University; Volgograd Medical Research Center

Email: a.brigadirova@gmail.com
ORCID iD: 0000-0003-0957-7087

Candidate of Sciences (Medicine), Associate Professor, Pharmacology and Bioinformatics Department, Volgograd State Medical University; Volgograd Medical Research Center

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 1, Pavshikh Bortsov Sq., Volgograd, 400131

Roman Litvinov

Volgograd State Medical University; Volgograd Medical Research Center

编辑信件的主要联系方式.
Email: litvinov.volggmu@mail.ru
ORCID iD: 0000-0002-0162-0653

Candidate of Sciences (Medicine), Senior researcher of the Metabotropic drugs Laboratory, Volgograd State Medical University; Researcher of the Laboratory of Experimental Pharmacology, Volgograd Medical Research Center

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 1, Pavshikh Bortsov Sq., Volgograd, 400131

Natalia Gurova

Volgograd State Medical University

Email: gurova.vlgmed@mail.ru
ORCID iD: 0000-0002-0670-1444

Doctor of Sciences (Medicine), Professor of the Pharmacology and Bioinformatics Department

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131

Alexey Smirnov

Volgograd State Medical University; Volgograd Medical Research Center

Email: alexey-smirnov@rambler.ru
ORCID iD: 0000-0001-5351-6105

Doctor of Sciences (Medicine), Head of the Pathological Anatomy Department, Volgograd State Medical University

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131; 1, Pavshikh Bortsov Sq., Volgograd, 400131

Nicolay Pan’shin

Volgograd State Medical University

Email: panshin.nickolay@gmail.com
ORCID iD: 0000-0002-4035-4108

Candidate of Sciences (Medicine), Associate Professor, Pathological Anatomy Department

俄罗斯联邦, 1, Pavshikh Bortsov Sq., Volgograd, 400131

Haider Abbas

Institute of Physical and Organic Chemistry, Southern Federal University

Email: vip.haider89@gmail.ru

Master’s student of the Organic Synthesis Laboratory

俄罗斯联邦, Bldg 2, 194, Stachki Ave., Rostov-on-Don, 344090

Anatoliy Morkovnik

Institute of Physical and Organic Chemistry, Southern Federal University

Email: asmork@mail.ru
ORCID iD: 0000-0002-9182-6101

Doctor of Sciences (Chemistry), Chief Researcher, Organic Synthesis Laboratory

俄罗斯联邦, Bldg 2, 194, Stachki Ave., Rostov-on-Don, 344090

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2. Figure 1 – Synthesis scheme for preparation of 9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole hydrochloride (DF-5)

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3. Figure 2 – Chemical structure of ALT-711 (alagebrium)

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4. Figure 3 – Glomerular histopathology. Effect of diabetes and either DF-5 or ALT-711 on kidney tissues

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5. Figure 4 – Effect of diabetes and either DF-5 or ALT-711 on renal AGEs accumulation

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版权所有 © Spasov A., Zhukovskaya O., Rashchenko A., Brigadirova A., Litvinov R., Gurova N., Smirnov A., Pan’shin N., Abbas H., Morkovnik A., 2023

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