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Toxicity of Evodiae fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition
Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produ...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271464/ https://www.ncbi.nlm.nih.gov/pubmed/25521117 http://dx.doi.org/10.3390/molecules191221168 |
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author | Cai, Qingyan Wei, Jingjing Zhao, Wei Shi, Si Zhang, Yu Wei, Renrong Zhang, Yue Li, Weirong Wang, Qi |
author_facet | Cai, Qingyan Wei, Jingjing Zhao, Wei Shi, Si Zhang, Yu Wei, Renrong Zhang, Yue Li, Weirong Wang, Qi |
author_sort | Cai, Qingyan |
collection | PubMed |
description | Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produce obvious cumulative hepatotoxicity, the mechanism behind this toxicity is still uncertain. In the present study, we investigated the influence of EF on oxidative stress, mitochondrial permeability transition, adenosine triphosphate (ATP), and cytochrome C release of hepatic mitochondria. Rats were divided into four groups and fed distilled water, 6, 12, 24 g/kg of aqueous extract of EF daily for 15 days. Evodiamine, rutaecarpine and evodine were quantified in the aqueous extract by high performance liquid chromatography with ultraviolet detection (HPLC/UV). The results showed that aqueous extract of EF could significantly (p < 0.05) decrease MnSOD levels to 56.50%, 46.77% and 19.67% of control group, GSH level was decreased to 74.24%, 53.97% and 47.91% of control group and MDA level was increased to 131.55%, 134.34% and 150.81% of control group in the 6, 12 and 24 g/kg groups, respectively; extract also induced mitochondria swelling, vacuolation, MPT pore opening and a significant decrease (p < 0.05) in mitochondrial potential, while ATP levels were significant decreased (p < 0.05) to 65.24%, 38.08% and 34.59% of control group in the 6, 12 and 24 g/kg groups, respectively, resulting in ATP depletion and CytC release, finally trigger cell death signaling, which are the partial hepatotoxicity mechanisms of EF. |
format | Online Article Text |
id | pubmed-6271464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62714642018-12-28 Toxicity of Evodiae fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition Cai, Qingyan Wei, Jingjing Zhao, Wei Shi, Si Zhang, Yu Wei, Renrong Zhang, Yue Li, Weirong Wang, Qi Molecules Article Evodiae fructus (EF) has been used in China for thousands of years as an analgesic, antiemetic, anti-inflammatory and antidiarrheal drug. EF is a toxic drug and causes hepatotoxicity in humans. Although recent chronic toxicity studies performed on aqueous extract of EF has revealed that it can produce obvious cumulative hepatotoxicity, the mechanism behind this toxicity is still uncertain. In the present study, we investigated the influence of EF on oxidative stress, mitochondrial permeability transition, adenosine triphosphate (ATP), and cytochrome C release of hepatic mitochondria. Rats were divided into four groups and fed distilled water, 6, 12, 24 g/kg of aqueous extract of EF daily for 15 days. Evodiamine, rutaecarpine and evodine were quantified in the aqueous extract by high performance liquid chromatography with ultraviolet detection (HPLC/UV). The results showed that aqueous extract of EF could significantly (p < 0.05) decrease MnSOD levels to 56.50%, 46.77% and 19.67% of control group, GSH level was decreased to 74.24%, 53.97% and 47.91% of control group and MDA level was increased to 131.55%, 134.34% and 150.81% of control group in the 6, 12 and 24 g/kg groups, respectively; extract also induced mitochondria swelling, vacuolation, MPT pore opening and a significant decrease (p < 0.05) in mitochondrial potential, while ATP levels were significant decreased (p < 0.05) to 65.24%, 38.08% and 34.59% of control group in the 6, 12 and 24 g/kg groups, respectively, resulting in ATP depletion and CytC release, finally trigger cell death signaling, which are the partial hepatotoxicity mechanisms of EF. MDPI 2014-12-16 /pmc/articles/PMC6271464/ /pubmed/25521117 http://dx.doi.org/10.3390/molecules191221168 Text en © 2014 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 license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cai, Qingyan Wei, Jingjing Zhao, Wei Shi, Si Zhang, Yu Wei, Renrong Zhang, Yue Li, Weirong Wang, Qi Toxicity of Evodiae fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition |
title | Toxicity of Evodiae
fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition |
title_full | Toxicity of Evodiae
fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition |
title_fullStr | Toxicity of Evodiae
fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition |
title_full_unstemmed | Toxicity of Evodiae
fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition |
title_short | Toxicity of Evodiae
fructus on Rat Liver Mitochondria: The Role of Oxidative Stress and Mitochondrial Permeability Transition |
title_sort | toxicity of evodiae
fructus on rat liver mitochondria: the role of oxidative stress and mitochondrial permeability transition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271464/ https://www.ncbi.nlm.nih.gov/pubmed/25521117 http://dx.doi.org/10.3390/molecules191221168 |
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