Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders

Пахомова, А. В.; Nebolsin, Vladimir E.; Першина, О. В.; Krupin, V. A.; Sandrikina, Lubov; Pan, Edgar; Ермакова, Н. Н.; Vaizova, O. E.; Widera, Darius; Grimm, Wolf-Dieter; Kravtsov, Viacheslav; Afanasiev, S. A.; Morozov, Sergey G.; Кубатиев, Аслан Амирханович; Дыгай, А. М.; Скурихин, Е. Г.

doi:10.3390/ijms21030991

Cited by 5 publications

(14 citation statements)

References 39 publications

(42 reference statements)

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“…The volume of administration was determined according to body weight. The Treamid dose was selected according to previous reports [16][17][18]. Treamid was administered in a therapeutic setting beginning at day 14 (d14) to assess the effect of the drug on the fibrotic phase of BLM model mice.…”

Section: Modeling Of Experimental Pulmonary Fibrosismentioning

confidence: 99%

“…Treamid was used at a concentration of 10 −7 M in vitro as described earlier [18], where Treamid was titrated to determine the optimal concentration in culture.…”

Section: Experimental Groupsmentioning

confidence: 99%

“…Recently, we have shown that Treamid can chelate metal ions including zinc, copper, iron, magnesium, and calcium [16,17]. Treamid has regenerative properties and restores the function of various tissues and organs [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Antifibrotic and Regenerative Effects of Treamid in Pulmonary Fibrosis

Скурихин

Nebolsin²,

Widera

et al. 2020

IJMS

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by interstitial fibrosis and progressive respiratory failure. Pirfenidone and nintedanib slow down but do not stop the progression of IPF. Thus, new compounds with high antifibrotic activity and simultaneously regenerative activity are an unmet clinical need. Recently, we showed that Treamid can help restoring the pancreas and testicular tissue in mice with metabolic disorders. We hypothesized that Treamid may be effective in antifibrotic therapy and regeneration of damaged lung tissue in pulmonary fibrosis. In this study, experiments were performed on male C57BL/6 mice with bleomycin-induced pulmonary fibrosis. We applied histological and immunohistochemical methods, ELISA, and assessed the expression of markers of endothelial and epithelial cells in primary cultures of CD31+ and CD326+ lung cells. Finally, we evaluated esterase activity and apoptosis of lung cells in vitro. Our data indicate that Treamid exhibits antifibrotic activity in mice with pulmonary fibrosis and has a positive effect on capillaries of the lungs. Treamid also increases the number of endothelial progenitor cells in the lungs of animals with pulmonary fibrosis. Lastly, Treamid increases esterase activity and decreases apoptosis of CD31+ lung cells in vitro. Based on these findings, we suggest that Treamid may represent a promising compound for the development of new antifibrotic agents, which are capable of stimulating regeneration of lung endothelium in IPF patients.

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Section: Modeling Of Experimental Pulmonary Fibrosismentioning

confidence: 99%

“…Treamid was used at a concentration of 10 −7 M in vitro as described earlier [18], where Treamid was titrated to determine the optimal concentration in culture.…”

Section: Experimental Groupsmentioning

confidence: 99%

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Antifibrotic and Regenerative Effects of Treamid in Pulmonary Fibrosis

Скурихин

Nebolsin²,

Widera

et al. 2020

IJMS

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“…BDDA or Treamid (XC268BG), chemical formula N1,N5-bis [2-(1H-imidazole-2-Il)ethyl]glutaramide (Figure 2), was kindly provided by PHARMENTERPRISES Ltd. (Nebolsin et al, 2016(Nebolsin et al, , 2018Pakhomova et al, 2020). BDDA was dissolved in 0.5% carboxymethylcellulose solution (vehicle).…”

Section: Bddamentioning

confidence: 99%

“…Derivatives of bisamides of dicarboxylic acids including bisamide derivative of dicarboxylic acid (BDDA) can chelate metal ions including zinc, copper, iron, magnesium, and calcium (Nebolsin et al, 2016(Nebolsin et al, , 2018. Based on our previous studies showing that BDDA has regenerative properties and restores the function of multiple tissues and organs (Nebolsin et al, 2016(Nebolsin et al, , 2018Pakhomova et al, 2020), we aimed to assess the efficacy of BDDA on hypogonadism resulting from MD in male C57BL/6 mice. The effects of BDDA on testicular stem and progenitor cells were evaluated in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 99%

Bisamide Derivative of Dicarboxylic Acid Contributes to Restoration of Testicular Tissue Function and Influences Spermatogonial Stem Cells in Metabolic Disorders

Пахомова

Першина

Nebolsin³

et al. 2020

Front. Cell Dev. Biol.

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Metabolic syndrome can lead to several challenging complications including degeneration of the pancreas and hypogonadism. Recently, we have shown that Bisamide Derivative of Dicarboxylic Acid (BDDA) can contribute to pancreatic restoration in mice with metabolic disorders via its positive effects on lipid and glucose metabolism, and by increasing the numbers of pancreatic stem cells. In the present study, we hypothesized that BDDA might also be effective in restoring hypogonadism caused by metabolic syndrome. Experiments were performed on male C57BL/6 mice with hypogonadism, where metabolic disorders have been introduced by a combination of streptozotocin treatment and high fat diet. Using a combination of histological and biochemical methods along with a flow cytometric analysis of stem and progenitor cell markers, we evaluated the biological effects of BDDA on testicular tissue, germ cells, spermatogonial stem cells in vitro and in vivo, as well as on fertility. We demonstrate that in mice with metabolic disorders, BDDA has positive effects on spermatogenesis and restores fertility. We also show that BDDA exerts its therapeutic effects by reducing inflammation and by modulating spermatogonial stem cells. Thus, our results suggest that BDDA could represent a promising lead compound for the development of novel therapeutics able to stimulate regeneration of the testicular tissue and to restore fertility in hypogonadism resulting from complications of metabolic syndrome.

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