Olaquindox

Reactive oxygen species-dependent JNK downregulated olaquindox-induced autophagy in HepG2 cells.[Pubmed: 25042557]

J Appl Toxicol. 2015 Jul;35(7):709-16.

Autophagy plays an important role in response to intracellular and extracellular stress to sustain cell survival. However, dysregulated or excessive autophagy may lead to cell death, known as "type II programmed cell death," and it is closely associated with apoptosis. In our previous study, we proposed that Olaquindox induced apoptosis of HepG2 cells through a caspase-9 dependent mitochondrial pathway.
METHODS AND RESULTS:
In this study, we investigated autophagy induced by Olaquindox and explored the crosstalk between apoptosis and autophagy in Olaquindox-treated HepG2 cells. Olaquindox-induced autophagy was demonstrated by the accumulation of monodansylcadervarine, as well as elevated expression of autophagy-related MAP-LC3 and Beclin 1 proteins. The autophagy inhibitor 3-methyladenine significantly increased the apoptotic rate induced by Olaquindox, which was correlated with increased ratio of Bax/Bcl-2. The further studies showed that Olaquindox increased the levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) effectively blocked the accumulation of ROS but failed to block autophagy. Moreover, Olaquindox induced the activation of c-Jun N-terminal protein kinase (JNK), and JNK inhibitor SP600125 failed to block autophagy. Instead, Olaquindox-induced autophagy was enhanced by NAC or SP600125. Meanwhile, JNK activation was remarkably blocked by NAC, indicating that ROS may be the upstream signaling molecules of JNK activation and involved in the negative regulation of Olaquindox-induced autophagy.
CONCLUSIONS:
These results suggest that Olaquindox induces autophagy in HepG2 cells and that Olaquindox-induced apoptosis can be enhanced by 3-methyladenine. Olaquindox-induced autophagy in HepG2 cells is upregulated by Beclin 1 but downregulated by ROS-dependent JNK.

Development of an on-line molecularly imprinted chemiluminescence sensor for determination of trace olaquindox in chick feeds.[Pubmed: 22505192]

J Sci Food Agric. 2012 Oct;92(13):2696-702.

Olaquindox, as one of the antimicrobial growth accelerants, is usually used in livestock production to improve feed efficiency. Due to health concerns over possible carcinogenic, mutagenic and photoallergenic effects of Olaquindox on animals, the development of simple, rapid and sensitive analytical method for determination of Olaquindox is crucial and necessary.
METHODS AND RESULTS:
In this study, a surface molecularly imprinted polymer was prepared by a molecular imprinting technique in combination with a sol-gel process using activated silica gel as a support material. This imprinted material exhibited with good recognition and selective ability, and fast adsorption-desorption dynamics toward Olaquindox. Using it as the recognition element, a new on-line molecularly imprinted solid phase extraction coupled with chemiluminescence sensor for the determination of Olaquindox was developed. The factors affecting preconcentration of the analytes and sensitivity of the method were all investigated. Under the optimal condition, the linear range of the calibration graph was between 2 × 10(-8) and 1 × 10(-6) g mL(-1) , and the detection limit of this method was 7 × 10(-9) g mL(-1) . The blank chick feed samples spiked with Olaquindox at 0.3, 0.9 and 1.5 μg g(-1) levels were extracted and determined by this presented method with recoveries ranging from 87% to 94%. This method was validated by high-performance liquid chromatography and the results correlated well with those obtained by both methods. Moreover, this method was quantitatively analysed with two contaminated chick feed samples.
CONCLUSIONS:
This study will provide a sensitive and fast method for the monitoring of Olaquindox residues in foods.

Olaquindox-induced apoptosis is suppressed through p38 MAPK and ROS-mediated JNK pathways in HepG2 cells.[Pubmed: 23812630]

Cell Biol Toxicol. 2013 Aug;29(4):229-38.

METHODS AND RESULTS:
We investigated mitogen-activated protein kinase (MAPK) pathways as well as reactive oxygen species (ROS) in Olaquindox-induced apoptosis. Exposure of HepG2 cells to Olaquindox resulted in the phosphorylation of p38 MAPK and c-Jun N-terminal kinases (JNK). To confirm the role of p38 MAPK and JNK, HepG2 cells were pretreated with MAPKs-specific inhibitors prior to Olaquindox treatment. Olaquindox-induced apoptosis was significantly potentiated by the JNK inhibitor (SP600125) or the p38 MAPK inhibitor (SB203580). Furthermore, we observed that Olaquindox treatment led to ROS generation and that Olaquindox-induced apoptosis and ROS generation were both significantly reduced by the antioxidants, superoxide dismutase and catalase. In addition, the levels of phosphorylation of JNK, but not p38 MAPK, were significantly suppressed after pretreatment of the antioxidants, while inhibition of the activations of JNK or p38 MAPK had no effect on ROS generation.
CONCLUSIONS:
This result suggested that ROS may be the upstream mediator for the activation of JNK. Conclusively, our results suggested that apoptosis in response to Olaquindox treatment in HepG2 cells might be suppressed through p38 MAPK and ROS-JNK pathways.

Genotoxicity of quinocetone, cyadox and olaquindox in vitro and in vivo.[Pubmed: 23774262]

Food Chem Toxicol. 2013 Sep;59:207-14.

Quinocetone (QCT) and Cyadox (CYA) are important derivative of heterocyclic N-oxide quinoxaline (QdNO), used actively as antimicrobial feed additives in China.
METHODS AND RESULTS:
Here, we tested and compared the genotoxic potential of QCT and CYA with Olaquindox (OLA) in Ames test, HGPRT gene mutation (HGM) test in V79 cells, unscheduled DNA synthesis (UDS) assay in human peripheral lymphocytes, chromosome aberration (CA) test, and micronucleus (MN) test in mice bone marrow. OLA was found genotoxic in all 5 assays. In Ames test, QCT produced His(+) mutants at 6.9 μg/plate in Salmonella typhimurium TA 97, at 18.2 μg/plate in TA 100, TA 1535, TA 1537, and at 50 μg/plate in TA 98. CYA produced His(+) mutants at 18.2 μg/plate in TA 97, TA 1535, and at 50 μg/plate in TA 98, TA 100 and TA 1537. QCT was found positive in HGM and UDS assay at concentrations ≥10 μg/ml while negative results were reported in CA test and MN test.
CONCLUSIONS:
Collectively, we found that OLA was more genotoxic than QCT and CYA. Genotoxicity of QCT was found at higher concentration levels in Ames test, HGM and UDS assays while CYA showed weak mutagenic potential to bacterial cells in Ames test.