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Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice

Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant propertie...

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Autores principales: Dallner, Gustav, Bentinger, Magnus, Hussain, Shafaat, Sinha, Indranil, Yang, Jiangning, Schwank-Xu, Cheng, Zheng, Xiaowei, Swiezewska, Ewa, Brismar, Kerstin, Valladolid-Acebes, Ismael, Tekle, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301068/
https://www.ncbi.nlm.nih.gov/pubmed/34356303
http://dx.doi.org/10.3390/antiox10071070
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author Dallner, Gustav
Bentinger, Magnus
Hussain, Shafaat
Sinha, Indranil
Yang, Jiangning
Schwank-Xu, Cheng
Zheng, Xiaowei
Swiezewska, Ewa
Brismar, Kerstin
Valladolid-Acebes, Ismael
Tekle, Michael
author_facet Dallner, Gustav
Bentinger, Magnus
Hussain, Shafaat
Sinha, Indranil
Yang, Jiangning
Schwank-Xu, Cheng
Zheng, Xiaowei
Swiezewska, Ewa
Brismar, Kerstin
Valladolid-Acebes, Ismael
Tekle, Michael
author_sort Dallner, Gustav
collection PubMed
description Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions. Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3β is a modified form of the naturally occurring tocotrienol-β. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications. Deh-T3β was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3β improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3β exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial function are involved, which are central to reducing diabetes complications.
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spelling pubmed-83010682021-07-24 Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice Dallner, Gustav Bentinger, Magnus Hussain, Shafaat Sinha, Indranil Yang, Jiangning Schwank-Xu, Cheng Zheng, Xiaowei Swiezewska, Ewa Brismar, Kerstin Valladolid-Acebes, Ismael Tekle, Michael Antioxidants (Basel) Article Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions. Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3β is a modified form of the naturally occurring tocotrienol-β. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications. Deh-T3β was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3β improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3β exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial function are involved, which are central to reducing diabetes complications. MDPI 2021-07-02 /pmc/articles/PMC8301068/ /pubmed/34356303 http://dx.doi.org/10.3390/antiox10071070 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
Dallner, Gustav
Bentinger, Magnus
Hussain, Shafaat
Sinha, Indranil
Yang, Jiangning
Schwank-Xu, Cheng
Zheng, Xiaowei
Swiezewska, Ewa
Brismar, Kerstin
Valladolid-Acebes, Ismael
Tekle, Michael
Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice
title Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice
title_full Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice
title_fullStr Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice
title_full_unstemmed Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice
title_short Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice
title_sort dehydro-tocotrienol-β counteracts oxidative-stress-induced diabetes complications in db/db mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301068/
https://www.ncbi.nlm.nih.gov/pubmed/34356303
http://dx.doi.org/10.3390/antiox10071070
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