Back to Search Start Over

Metabolites and JAK/STAT pathway were involved in the liver and spleen damage in male Wistar rats fed with mequindox

Authors :
Wang, Xu
Huang, Xian-Ju
Ihsan, Awais
Liu, Zhao-Ying
Huang, Ling-Li
Zhang, Hua-Hai
Zhang, Hong-Fei
Zhou, Wen
Liu, Qin
Xue, Xi-Juan
Yuan, Zong-Hui
Source :
Toxicology. Feb2011, Vol. 280 Issue 3, p126-134. 9p.
Publication Year :
2011

Abstract

Abstract: Mequindox (MEQ) is a novel synthetic quinoxaline 1,4-dioxides antibacterial agent and growth promoter in animal husbandry. This study was to investigate whether reactive oxygen species (ROS), the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway, suppressors of cytokine signaling (SOCS) and inflammatory cytokines were involved in toxicities of MEQ. Our data demonstrated that high dose of MEQ (275mg/kg) apparently led to tissue impairment combined with imbalance of redox in liver. In liver and spleen samples, hydroxylation metabolites and desoxymequindox were detected, directly confirming the potential link of N→O group reduction metabolism with its organ toxicity. Moreover, up-regulation of JAK/STAT, SOCS family, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were also observed in the high-dose group. Meanwhile, significant changes of oxidative stress indices in liver were observed in the high-dose group. As for NADPH subunit, the mRNA levels of many subunits were significantly up-regulated at low doses but down-regulated in a dose-dependent manner in liver and spleen, suggesting an involvement of NADPH in MEQ metabolism and ROS generation. In conclusion, we reported the dose-dependent long-term toxicity as well as the discussion of the potential mechanism and pathways of MEQ, which raised further awareness of its toxicity following with the dose change. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
0300483X
Volume :
280
Issue :
3
Database :
Academic Search Index
Journal :
Toxicology
Publication Type :
Academic Journal
Accession number :
57683692
Full Text :
https://doi.org/10.1016/j.tox.2010.12.001