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RP11 Immune and Endocrine Disruption: Detection and Implication
(RIC-1117-821084) The effects of acute exposure to Indirubin-3-monoxime on lymphoid CYP1A expression and select immune functions in channel catfish.
Babcock, A1, Rice, C1, 1 CIET/Biological Sciences, Clemson University, Clemson, SC, USA
ABSTRACT- Indirubin (IR) is an indole metabolite of tryptophan and is the active anti-neoplastic ingredient in extracts from the Chinese herb Polygonum tinctgorium. At least in mammalian systems, indirubin binds to the cytosolic aryl hydrocarbon receptor (AhR) with high affinity and activates the translocation of the ligand-receptor complex to the nucleus, leading to gene activation. Several studies suggest that tryptophan and its metabolites may be the endogenous ligand for the AhR. Moreover, it is now known that tryptophan levels have dramatic effects on antigen-specific immunity in vertebrates. However, immunotoxicologists have established that virtually any xenobiotic that binds to the AhR with high affinity (e.g., TCDD and co-planar PCBs) modulate immune functions in a variety of animal models. We exposed channel catfish to 3 mM/kg IR, PCB-126, or carrier control via a single i.p. injection and three days later examined lymphoid CYP1A induction and quantified circulating lysozyme, total IgM, C-reactive protein levels. Compared to fish receiving carrier control, only PCB-126 treatment induced lymphoid CYP1A, while both IR and PCB-126 suppressed circulating lysozyme and IgM. C-reactive protein was not altered by either treatment. This study suggests that indirubin may be a potent immunotoxic compound and that channel catfish are useful models for further studying its effects on immune functions in vertebrates. However, based on lymphoid CYP1A as in indicator of AhR binding and activation, it appears that IR may not be as potent as PCB-126 in fish. A critical step in further characterizing the AhR-binding and activation potential of IR in fish will be to examine hepatic CYP1A and to further evaluate dose-response relationships over longer periods of time.
Key words: indirubin, channel catfish, aryl hydrocarbon receptor, immunotoxicity
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