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