Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat.

نویسندگان

  • Natalya Hanlon
  • Nick Coldham
  • Adriana Gielbert
  • Nikolai Kuhnert
  • Maurice J Sauer
  • Laurie J King
  • Costas Ioannides
چکیده

Sulforaphane is a naturally occurring isothiocyanate with promising chemopreventive activity. An analytical method, utilising liquid chromatography-MS/MS, which allows the determination of sulforaphane in small volumes of rat plasma following exposure to low dietary doses, was developed and validated, and employed to determine its absolute bioavailability and pharmacokinetic characteristics. Rats were treated with either a single intravenous dose of sulforaphane (2.8 micromol/kg) or single oral doses of 2.8, 5.6 and 28 mumol/kg. Sulforaphane plasma concentrations were determined in blood samples withdrawn from the rat tail at regular time intervals. Following intravenous administration, the plasma profile of sulforaphane was best described by a two-compartment pharmacokinetic model, with a prolonged terminal phase. Sulforaphane was very well and rapidly absorbed and displayed an absolute bioavailability of 82 %, which, however, decreased at the higher doses, indicating a dose-dependent pharmacokinetic behaviour; similarly, Cmax values did not rise proportionately to the dose. At the highest dose used, the rate of absorption constant k(ab), biological half-life t(1/2) and apparent volume of distribution decreased significantly. It is concluded that in the rat orally administered sulforaphane is rapidly absorbed, achieving high absolute bioavailability at low dietary doses, but dose-dependent pharmacokinetics was evident, with bioavailability decreasing with increasing dose.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane.

Glucosinolates (GL) can inhibit, retard or reverse experimental multistage carcinogenesis. When brassica plant tissue is broken, GLs are hydrolyzed by the endogenous enzyme myrosinase (Myr), releasing many products including isothiocyanates (ITC). Synthetic ITCs like sulforaphane exert chemopreventive effects against chemically induced tumors in animals, modulating enzymes required for carcinog...

متن کامل

اثر سولفورافن بر رگ‌زایی در پرده کوریو الانتوئیک جوجه و بررسی فعالیت آنتی‌اکسیدانی آن

Background and Aim: Sulforaphane is a type of isothiocyanate with anticancer effects. In the present study, the effect of sulforaphane in angiogenesis in chicks' chorioallantoic membrane was investigated. Materials and Methods: In this experimental study, a total of 56 fertilized eggs were divided into 7 groups of eight with three replications: control, control-Experimental and five treatment...

متن کامل

Pharmacokinetics of rosmarinic acid in rats by LC-MS/MS: absolute bioavailability and dose proportionality

Rosmarinic acid (RA), one of the main bioactive compounds of Rosmarinus officinalis L., exhibits diverse pharmacological effects. However, its oral absolute bioavailability and dose proportionality in vivo have not been comprehensively studied. In the present study, a validated LC-MS/MS method was developed for the determination of RA in rat plasma. Pharmacokinetic parameters were obtained foll...

متن کامل

Comparative Bioavailability of Ranitidine Tablets in Healthy Volunteers

The pharmacokinetic parameters of domestic and imported ranitidine hydrochloride tablets (Ranitidine, formulated and manufactured by Kharazmi Pharmaceuticals, Iran, and Zantac ? manufactured by Glaxo, UK) were measured in 14 healthy subjects following oral administration of a single 300-mg dose of each brand and compared for bioequivalence evaluation. The pharmaceutical equivalency of both fo...

متن کامل

Sulforaphane suppresses polycomb group protein level via a proteasome-dependent mechanism in skin cancer cells.

The polycomb group (PcG) genes encode a family of proteins that methylate and ubiquitinate histones to close chromatin and suppress gene expression. PcG proteins are present at elevated levels in cancer cells, and this is associated with reduced tumor suppressor protein level and enhanced cell survival. Agents that reduce PcG protein level are regarded as potentially cancer-preventative agents....

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The British journal of nutrition

دوره 99 3  شماره 

صفحات  -

تاریخ انتشار 2008