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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8230275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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