Document Detail


ROS mediated cytotoxicity of porcine adrenocortical cells induced by QdNOs derivatives in vitro.
MedLine Citation:
PMID:  20188712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Quinoxaline 1,4-dioxides (QdNOs) derivatives, the potent synthetic antibacterial group used in food-producing animals, are assumed to have pro-oxidant properties. However, how oxidative stress mediated their adrenal toxicity is far from clear. The aim of this study was to assess the ability of three QdNOs, i.e. olaquindox (OLA), mequindox (MEQ), and cyadox (CYA), to produce reactive oxygen species (ROS) and oxidative cell damage in porcine adrenocortical cells. Multiple approaches such as cell activity assay, biochemical detectation, flow cytometry and fluorescent were used to study the integrated role of ROS homeostasis, mitochondrial redox metabolism and cell apoptosis as well as chemical stability of these drugs. The results showed that OLA and MEQ treatment evoked a significant dose and time-dependent cell damage in adrenocortical cells, well CYA displayed much less toxicity. As for the intracellular ROS production, OLA irritated a persistent and utmost release of ROS while MEQ made a similar but weaker reaction. CYA, however, had a short and unstable release of intracellular ROS. On the other hand, quinoxalinine-2-carboxylie acid (QCA), one of the metabolites of OLA and MEQ, did not cause any significant production of ROS and showed relatively lower toxicity than its parents. Moreover, an imbalance in the redox metabolism and mitochondrial membrane damage has been implicated in adrenal toxicity of QdNOs. ROS scavengers partially reversed QdNOs-induced mitochondrial damage, indicating that mitochondria may be a major target and critical for ROS-mediated cell death. In a word, these results suggested that ROS is a key mediator of QdNOs-induced cell death via mitochondria-dependent pathway in adrenocortical cells. The results provide a mechanism approach in understanding the characterize of adrenal damage caused by QdNOs in vitro, which would in turn, help in designing the appropriate therapeutic strategies of these kind of feed additives.
Authors:
Xian-Ju Huang; Hua-Hai Zhang; Xu Wang; Ling-Li Huang; Ling-Yan Zhang; Cai-Xia Yan; Yu Liu; Zong-Hui Yuan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-25
Journal Detail:
Title:  Chemico-biological interactions     Volume:  185     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-05-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  227-34     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
National Reference Laboratory of Veterinary Drug Residues (HZAU)/MOA Key Laboratory of Food Safety Evaluation, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. huangxj554@sohu.com
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MeSH Terms
Descriptor/Qualifier:
Adrenal Cortex / cytology,  drug effects*
Animals
Apoptosis / drug effects
Cell Death / drug effects
Cell Survival / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Mitochondria / metabolism
Molecular Structure
Oxidation-Reduction
Quinoxalines / chemistry,  pharmacology*
Reactive Oxygen Species / metabolism*
Swine
Time Factors
Chemical
Reg. No./Substance:
0/Mequindox; 0/Quinoxalines; 0/Reactive Oxygen Species; 23696-28-8/olaquindox; 65884-46-0/cyadox

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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