کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9036572 1133346 2005 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues
چکیده انگلیسی
Sanguinarine's use in human clinical applications is currently controversial. While some studies have demonstrated sanguinarine's anti-inflammatory and anti-oxidant properties, other investigations reported sanguinarine's procarcinogenic effects. Like the tobacco-associated carcinogen, benzo(a)pyrene (B(a)P), sanguinarine is a polycyclic aromatic hydrocarbon (PAH). PAH exposure activates the aryl hydrocarbon transcription activating factor (AhR), resulting in nuclear translocation, binding to the aryl hydrocarbon nuclear translocator (ARNT), which thereby increases expression of a pool of carcinogen metabolizing enzymes. The goal of this study was to investigate whether sanguinarine activates this PAH-associated signaling cascade in human oral cells and tissues. Our results demonstrate that sanguinarine: (i) results in formation of the AhR-ARNT complex, (ii) induces AhR-associated gene expression, (iii) inhibits cytochrome P450 1A1 (CYP 1A1) microsomal oxidative activity and (iv) pretreatment upregulates CYP 1A1 function. Collectively, these data provide evidence that sanguinarine activates PAH-associated signaling and metabolic pathways. Notably, previous studies have demonstrated that mammalian hepatic microsomes metabolize sanguinarine to a mutagenic epoxide. Persons who respond to sanguinarine exposure with induction of primarily Phase I relative to Phase II enzymes are, therefore, at risk for sanguinarine bioactivation and its potential mutagenic effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 158, Issue 1, 28 July 2005, Pages 50-60
نویسندگان
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