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Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats
Mitochondrial impairment ensuing from oxidative imbalance is related to adverse consequences of bisphenol A (BPA), a globally utilized industrial chemical. Recent evidence reveals sirtuin 3 (SIRT3) as a key regulator of mitochondrial homeostasis; however, its role in BPA toxicity remains unidentifie...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358790/ https://www.ncbi.nlm.nih.gov/pubmed/30641872 http://dx.doi.org/10.3390/ijms20020267 |
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author | Peerapanyasut, Wachirasek Kobroob, Anongporn Palee, Siripong Chattipakorn, Nipon Wongmekiat, Orawan |
author_facet | Peerapanyasut, Wachirasek Kobroob, Anongporn Palee, Siripong Chattipakorn, Nipon Wongmekiat, Orawan |
author_sort | Peerapanyasut, Wachirasek |
collection | PubMed |
description | Mitochondrial impairment ensuing from oxidative imbalance is related to adverse consequences of bisphenol A (BPA), a globally utilized industrial chemical. Recent evidence reveals sirtuin 3 (SIRT3) as a key regulator of mitochondrial homeostasis; however, its role in BPA toxicity remains unidentified. This study explored the potential benefits of N-acetylcysteine (NAC), an effective antioxidant, against BPA toxicity in the kidney and liver, and examined whether SIRT3 was involved in this condition. Male Wistar rats were fed with vehicle, BPA (5, 50 mg/kg), BPA (50 mg/kg) plus NAC (100 mg/kg) and were evaluated after 5 weeks. NAC treatment significantly diminished BPA-induced kidney and liver functional disorders, histopathological alterations, oxidative stress, and apoptosis. The increased mitochondrial reactive oxygen species, the disrupted membrane potential, the swelling, and the impaired mitochondrial fission caused by BPA were also mitigated upon concurrent treatment with NAC. The benefits of NAC were associated with enhanced AMPK-PGC-1α-SIRT3 signaling protein expressions, which led to decreased acetylation of superoxide dismutase 2 (SOD2) and increased expression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD). The findings demonstrate the efficacy of NAC in protecting BPA-induced kidney and liver injury, which, in part, is mediated by activating SIRT3 and improving mitochondrial function, dynamics, and oxidative imbalance. |
format | Online Article Text |
id | pubmed-6358790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63587902019-02-06 Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats Peerapanyasut, Wachirasek Kobroob, Anongporn Palee, Siripong Chattipakorn, Nipon Wongmekiat, Orawan Int J Mol Sci Article Mitochondrial impairment ensuing from oxidative imbalance is related to adverse consequences of bisphenol A (BPA), a globally utilized industrial chemical. Recent evidence reveals sirtuin 3 (SIRT3) as a key regulator of mitochondrial homeostasis; however, its role in BPA toxicity remains unidentified. This study explored the potential benefits of N-acetylcysteine (NAC), an effective antioxidant, against BPA toxicity in the kidney and liver, and examined whether SIRT3 was involved in this condition. Male Wistar rats were fed with vehicle, BPA (5, 50 mg/kg), BPA (50 mg/kg) plus NAC (100 mg/kg) and were evaluated after 5 weeks. NAC treatment significantly diminished BPA-induced kidney and liver functional disorders, histopathological alterations, oxidative stress, and apoptosis. The increased mitochondrial reactive oxygen species, the disrupted membrane potential, the swelling, and the impaired mitochondrial fission caused by BPA were also mitigated upon concurrent treatment with NAC. The benefits of NAC were associated with enhanced AMPK-PGC-1α-SIRT3 signaling protein expressions, which led to decreased acetylation of superoxide dismutase 2 (SOD2) and increased expression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD). The findings demonstrate the efficacy of NAC in protecting BPA-induced kidney and liver injury, which, in part, is mediated by activating SIRT3 and improving mitochondrial function, dynamics, and oxidative imbalance. MDPI 2019-01-11 /pmc/articles/PMC6358790/ /pubmed/30641872 http://dx.doi.org/10.3390/ijms20020267 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Peerapanyasut, Wachirasek Kobroob, Anongporn Palee, Siripong Chattipakorn, Nipon Wongmekiat, Orawan Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats |
title | Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats |
title_full | Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats |
title_fullStr | Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats |
title_full_unstemmed | Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats |
title_short | Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats |
title_sort | activation of sirtuin 3 and maintenance of mitochondrial integrity by n-acetylcysteine protects against bisphenol a-induced kidney and liver toxicity in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358790/ https://www.ncbi.nlm.nih.gov/pubmed/30641872 http://dx.doi.org/10.3390/ijms20020267 |
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