Abstract
Olaquindox, a quinoxaline 1,4-dioxide derivative, is widely used as a feed additive in many countries. The potential genotoxicity of olaquindox, hence, is of concern. However, the proper mechanism of toxicity was unclear. The aim of the present study was to investigate the effect of growth arrest and DNA damage 45 alpha (GADD45a) on olaquindox-induced DNA damage and cell cycle arrest in HepG2 cells. The results showed that olaquindox could induce reactive oxygen species (ROS)-mediated DNA damage and S-phase arrest, where increases of GADD45a, cyclin A, Cdk 2, p21 and p53 protein expression, decrease of cyclin D1 and the activation of phosphorylation-c-Jun N-terminal kinases (p-JNK), phosphorylation-p38 (p-p38) and phosphorylation-extracellular signal-regulated kinases (p-ERK) were involved. However, GADD45a knockdown cells treated with olaquindox could significantly decrease cell viability, exacerbate DNA damage and increase S-phase arrest, associated with the marked activation of p-JNK, p-p38, but not p-ERK. Furthermore, SP600125 and SB203580 aggravated olaquindox-induced DNA damage and S-phase arrest, suppressed the expression of GADD45a. Taken together, these findings revealed that GADD45a played a protective role in olaquindox treatment and JNK/p38 pathways may partly contribute to GADD45a regulated olaquindox-induced DNA damage and S-phase arrest. Our findings increase the understanding on the molecular mechanisms of olaquindox.
Highlights
Quinoxaline 1,4-dioxides (QdNOs) consisting of one or two acyclic chain moieties (Figure 1A), have many biological properties, such as antimicrobial, antitumora and anti-inflammatory actions [1,2,3].Olaquindox (Figure 1B) is one of the QdNOs family and it has been mainly used as a growth promotant.in 1999, The European Commission of the European Community has forbidden the use of olaquindox as a growth promotant due to its genotoxicity and potential risk [4]
S-phase arrest, suppressed the expression of growth arrest and DNA damage 45 alpha (GADD45a). These findings revealed that GADD45a played a protective role in olaquindox treatment and JNK/p38 pathways may partly contribute to GADD45a regulated olaquindox-induced DNA damage and S-phase arrest
Olaquindox is an important member of the quinoxaline family which is used as a feed additive
Summary
Olaquindox (Figure 1B) is one of the QdNOs family and it has been mainly used as a growth promotant. In 1999, The European Commission of the European Community has forbidden the use of olaquindox as a growth promotant due to its genotoxicity and potential risk [4]. Despite a lack of evidence of toxicity and underlying mechanisms, olaquindox has still been extensively used as a feed additive in swine to improve the efficiency of feed conversion [5]. Recently available data illustrated its potential adverse reaction such as genotoxicity and cytotoxicity [6,7], mutagenicity [8]. It have been demonstrated that olaquindox had obvious cumulative toxicity [10,11]. Human and animal health may be affected because of abuse of olaquindox, such as continuous feeding, irrational dosages, or unreasonable drug withdrawal periods
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
