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Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals

Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LH...

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Autores principales: Blinova, Ekaterina, Pakhomov, Dmitry, Shimanovsky, Denis, Kilmyashkina, Marina, Mazov, Yan, Demura, Tatiana, Drozdov, Vladimir, Blinov, Dmitry, Deryabina, Olga, Samishina, Elena, Butenko, Aleksandra, Skachilova, Sofia, Sokolov, Alexey, Vasilkina, Olga, Alkhatatneh, Bashar A., Vavilova, Olga, Sukhov, Andrey, Shmatok, Daniil, Sorokvasha, Ilya, Tumutolova, Oxana, Lobanova, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230275/
https://www.ncbi.nlm.nih.gov/pubmed/34205061
http://dx.doi.org/10.3390/biom11060834
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author Blinova, Ekaterina
Pakhomov, Dmitry
Shimanovsky, Denis
Kilmyashkina, Marina
Mazov, Yan
Demura, Tatiana
Drozdov, Vladimir
Blinov, Dmitry
Deryabina, Olga
Samishina, Elena
Butenko, Aleksandra
Skachilova, Sofia
Sokolov, Alexey
Vasilkina, Olga
Alkhatatneh, Bashar A.
Vavilova, Olga
Sukhov, Andrey
Shmatok, Daniil
Sorokvasha, Ilya
Tumutolova, Oxana
Lobanova, Elena
author_facet Blinova, Ekaterina
Pakhomov, Dmitry
Shimanovsky, Denis
Kilmyashkina, Marina
Mazov, Yan
Demura, Tatiana
Drozdov, Vladimir
Blinov, Dmitry
Deryabina, Olga
Samishina, Elena
Butenko, Aleksandra
Skachilova, Sofia
Sokolov, Alexey
Vasilkina, Olga
Alkhatatneh, Bashar A.
Vavilova, Olga
Sukhov, Andrey
Shmatok, Daniil
Sorokvasha, Ilya
Tumutolova, Oxana
Lobanova, Elena
author_sort Blinova, Ekaterina
collection PubMed
description Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl(6) mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db/db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA. Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties. Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.
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spelling pubmed-82302752021-06-26 Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals Blinova, Ekaterina Pakhomov, Dmitry Shimanovsky, Denis Kilmyashkina, Marina Mazov, Yan Demura, Tatiana Drozdov, Vladimir Blinov, Dmitry Deryabina, Olga Samishina, Elena Butenko, Aleksandra Skachilova, Sofia Sokolov, Alexey Vasilkina, Olga Alkhatatneh, Bashar A. Vavilova, Olga Sukhov, Andrey Shmatok, Daniil Sorokvasha, Ilya Tumutolova, Oxana Lobanova, Elena Biomolecules Article Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl(6) mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db/db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA. Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties. Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment. MDPI 2021-06-03 /pmc/articles/PMC8230275/ /pubmed/34205061 http://dx.doi.org/10.3390/biom11060834 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Blinova, Ekaterina
Pakhomov, Dmitry
Shimanovsky, Denis
Kilmyashkina, Marina
Mazov, Yan
Demura, Tatiana
Drozdov, Vladimir
Blinov, Dmitry
Deryabina, Olga
Samishina, Elena
Butenko, Aleksandra
Skachilova, Sofia
Sokolov, Alexey
Vasilkina, Olga
Alkhatatneh, Bashar A.
Vavilova, Olga
Sukhov, Andrey
Shmatok, Daniil
Sorokvasha, Ilya
Tumutolova, Oxana
Lobanova, Elena
Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals
title Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals
title_full Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals
title_fullStr Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals
title_full_unstemmed Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals
title_short Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals
title_sort cerium-containing n-acetyl-6-aminohexanoic acid formulation accelerates wound reparation in diabetic animals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230275/
https://www.ncbi.nlm.nih.gov/pubmed/34205061
http://dx.doi.org/10.3390/biom11060834
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