The metabolism of olaquindox in rats, chickens and pigs

Liu, Zhao‐Ying; Huang, Lingli; Zhou, Xiao-Ni; Chen, Dongmei; Yue, Tao; Zhang, Hua-Hai; Zhang, Yuan

doi:10.1016/j.toxlet.2010.10.010

Cited by 22 publications

(13 citation statements)

References 14 publications

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“…OLA has been shown to be mutagenic in a variety of test systems in vivo and in vitro, such as the Ames test with Salmonella typhimurium strains, Escherichia coli, micronucleus tests in the mouse and SOS chromotest (Beutin et al, 1981, Liu et al, 2011, Yoshimura et al, 1981. The mutagenicity was detected in the absence of an exogeneous mammalian enzyme activation system which is usually needed to activate a large number of indirect mutagens.…”

Section: Introductionmentioning

confidence: 99%

Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Yang

Jiang

She

et al. 2015

Environmental Toxicology and Pharmacology

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Section: Introductionmentioning

confidence: 99%

Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Yang

Jiang

She

et al. 2015

Environmental Toxicology and Pharmacology

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“…AO, acridine orange; cCBR1, chicken carbonyl reductase 1; porcine carbonyl reductase 1; SsAOX1, porcine aldehyde oxidase. Cited from (Chen et al, 2013;Huang et al, 2015bHuang et al, , 2015cLi et al, 2014aLi et al, , 2014bLiu et al, 2008Liu et al, , 2009Liu et al, , 2010aLiu et al, , 2010bLiu et al, , 2010cLiu et al, , 2011aLiu et al, , 2011bLiu & Sun, 2013;Mu et al, 2014;Tang et al, 2012;Wang et al, 2016b;Yang et al, 2013a;Zheng et al, 2011). marked as less genotoxicity than other kinds Wang et al, , 2011b.…”

Section: Resultsmentioning

confidence: 99%

“…Based on the same quinoxaline structure and different toxicity of QdNOs with different side chains, it was indicated that the side chains played crucial roles in their toxicity. The main metabolism of QdNOs in vivo was similar and it was N!O group reduction (Huang et al, 2015bLi et al, 2014aLi et al, , 2014bLiu et al, 2008Liu et al, , 2010aLiu et al, , 2010bLiu et al, , 2010cLiu et al, , 2011bLiu et al, , 2011bLiu & Sun, 2013). Then, it was presumed that the degree of difficulty in N!O group reduction will affect the toxic effects of QdNOs.…”

Section: Resultsmentioning

confidence: 99%

The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo

Wang

Martínez

Cheng

et al. 2016

Drug Metabolism Reviews

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Quinoxaline 1,4-dioxide derivatives (QdNOs) have been widely used as growth promoters and antibacterial agents. Carbadox (CBX), olaquindox (OLA), quinocetone (QCT), cyadox (CYA) and mequindox (MEQ) are the classical members of QdNOs. Some members of QdNOs are known to cause a variety of toxic effects. To date, however, almost no review has addressed the toxicity and metabolism of QdNOs in relation to oxidative stress. This review focused on the research progress associated with oxidative stress as a plausible mechanism for QdNO-induced toxicity and metabolism. The present review documented that the studies were performed over the past 10 years to interpret the generation of reactive oxygen species (ROS) and oxidative stress as the results of QdNO treatment and have correlated them with various types of QdNO toxicity, suggesting that oxidative stress plays critical roles in their toxicities. The major metabolic pathways of QdNOs are N→O group reduction and hydroxylation. Xanthine oxidoreductase (XOR), aldehyde oxidase (SsAOX1), carbonyl reductase (CBR1) and cytochrome P450 (CYP) enzymes were involved in the QdNOs metabolism. Further understanding the role of oxidative stress in QdNOs-induced toxicity will throw new light onto the use of antioxidants and scavengers of ROS as well as onto the blind spots of metabolism and the metabolizing enzymes of QdNOs. The present review might contribute to revealing the QdNOs toxicity, protecting against oxidative damage and helping to improve the rational use of concurrent drugs, while developing novel QdNO compounds with more efficient potentials and less toxic effects.

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“…Olaquindox could apparently affect human health due to potentially toxic residues in edible animal-origin products. In long-term toxicity studies of olaquindox in rats it has been demonstrated that toxic effects were detected in the kidney, liver and endocrine glands [ 5 ]. According to a new study, even at a relatively low concentration of olaquindox (6.6 μg/mL), significant mutagenic effects may result and the mutation frequency was increased by up to 12-fold [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

Zhao

Yang

et al. 2017

Molecules

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Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. The results revealed that olaquindox treatment reduced the cell viability of HEK293 cells and downregulated the expression of TSC2 in a dose- and time-dependent manner. Meanwhile, olaquindox treatment markedly induced the production of reactive oxygen species (ROS), cascaded to autophagy, oxidative stress, and apoptotic cell death, which was effectively eliminated by the antioxidant N-acetylcysteine (NAC). Furthermore, overexpression of TSC2 attenuated olaquindox-induced autophagy in contrast to inducing the production of ROS, oxidative stress and apoptosis. Consistently, knockdown of TSC2 upregulated autophagy, and decreased olaquindox-induced cell apoptosis. In conclusion, our findings indicate that TSC2 partly participates in olaquindox-induced autophagy, oxidative stress and apoptosis, and demonstrate that TSC2 has a negative regulation role in olaquindox-induced autophagy in HEK293 cells.

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The metabolism of olaquindox in rats, chickens and pigs

Cited by 22 publications

References 14 publications

Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

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