English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

An intestinal epithelium-specific cytochrome P450 (P450) reductase (CPR)-knockout (IE-Cpr-null) mouse and a liver-specific CPR-knockout (liver-Cpr-null) mouse were studied for determination of the respective roles of P450 enzymes in the liver and small intestine (SI) in the clearance of orally administered benzo[a]pyrene (BaP). Pharmacokinetic analysis of blood BaP levels indicated significantly lower rates of BaP clearance in IE-Cpr-null than in wild-type (WT) mice, after oral BaP (30 mg/kg) treatment. In contrast, clearance rates for intraperitoneal BaP (45 mg/kg) were not different between IE-Cpr-null and WT mice. Furthermore, there was no significant difference between liver-Cpr-null and WT mice in BaP clearance, after either intraperitoneal or oral BaP administration. Thus, small-intestinal P450-mediated first-pass metabolism is a key determinant of the systemic bioavailability of oral BaP. In addition, we observed greater differences in the rates of clearance of oral BaP, between WT and IE-Cpr-null mice, in mice pretreated with beta-naphthoflavone, to induce CYP1A1 expression, than in untreated mice. The onset of induction (at 2 h after dosing) of CYP1A1 protein expression by oral BaP administration was earlier in the SI than in extra-gut organs analyzed; for liver, lung, and kidney, induction was not observed until 4 h after dosing. Furthermore, BaP tissue burdens in SI and extra-gut organs of IE-Cpr-null mice were greater than burdens in corresponding organs of WT mice, at 6 or 24 h after BaP administration. Taken together, these findings strongly support the concept that small-intestinal CYP1A1 induction is a critical factor in protection against systemic exposure to oral BaP.

The Role of Small-Intestinal P450 Enzymes in Protection against Systemic Exposure of Orally Administered Benzo[a]Pyrene