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Y. Garfias, J. Aragón-Medrano, R. Tadayoni, R. Benard, J.-A. Sahel, A. Rendon; Cytochrome P450-1A1 Up-Regulation Is Absent in Mouse Retinas After Xenobiotic Beta-Naphtoflavone Treatment. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2909.
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Cytochrome P450 (CYP) is a multi-gene family encoding constitutive and inducible heme-containing enzymes. They are primarily found in liver and adrenal gland. The CYP1A1 isoform is inducible by xenobiotics through Aryl hydrocarbon Receptor-Aryl hydrocarbon nuclear translocator (Ahr/ARNT) mechanism for cellular detoxification. The role of xenobiotic beta-naphtoflavone (bNF) metabolism has been studied in specific organs such as liver, and brain. Here we aimed to determine its effect in retinal tissue.
Mouse hepatocarcinoma cell line (Hepa-1) was used to determine the expression of bNF CYP1A1 dependent mechanism; the cells were cultured for 24 with 50 µM of bNF. C57BL/6 adult mice were intra-peritoneally injected with 100 mg/kg of bNF dissolved in corn oil, after 24 h, liver and retinas were dissected and Western Blots were performed to detect CYP1A1.
In Hepa-1 cells there was a significantly increased of CYP1A1 after bNF treatment compared to controls. When mice were treated with bNF, there was also a significant increase of CYP1A1 expression in the bNF mice livers compared to the controls. There was no evidence of the CYP1A1 expression in retinas, neither when the mice were bNF treated. To determine whether blood retinal barrier is selective to this xenobiotic, we performed intra-vitreal injections of bNF and after 24 h, retinas were dissected and Western Blots were performed. There was no presence of CYP1A1.
These results indicate that the bNF actively induced the signaling pathway in vitro and in vivo systems; however, the retina is a tissue that does not respond to this chemical up-regulating CYP1A1. The possibility of AhR absence in retina or a new signaling pathway to metabolize this xenobiotic is still under study.
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