Broccoli and cancer protection.
Sulphorophane (SF) is a phytochemical found in high amounts in broccoli and broccoli sprouts. Since first being identified as having chemopreventative properties in the 1990s, it has been studied extensively and found to have multiple effects, including the induction of phase 2 cytoprotective enzymes via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation, as well as modulation of genes and processes involved in many stages of cancer induction. These include: alteration of susceptibility to carcinogens, cell cycle processes, cell death, angiogenesis, invasion, metastasis and cancer stem cell growth. In vitro studies have further confirmed the ability of SF to inhibit a wide variety of cancer cell lines including bladder, breast, colon, lung, pancreas, prostate, skin and stomach.
Increasingly, evidence is mounting that suggests that dietary SF may have more beneficial effects in some tissues than others, as it may reach different organs in differing concentrations. SF is initially metabolised via the mercapturic acid pathway in vivo, and experiments have shown that over 70% of orally administered SF in humans is eliminated via this pathway within 12-24 hours. Metabolites formed from the pathway are unstable and rapidly dissociate back to SF under physiological conditions. Some studies have shown levels of SF in urine that were markedly higher than those in plasma, suggesting that the bladder may be one organ that has higher levels of exposure to orally ingested SF.
In order to obtain some more clarity about the organ-specific effects of this compound, researchers designed the current study to examine in-vivo tissue exposure and response to dietary SF in a large number of organs. In order to do so, they exposed rats to both a control vehicle (soya oil) or SF at 150umol/kg (dissolved in soya oil), and then euthanized them at 1, 5, 6 and 24 hours post dose, with urine collections for the corresponding times and blood collection when the animals were killed. GST and NQO1 are two ubiquitously released cytoprotective phase 2 enzymes induced by SF, and thus were used as biomarkers of tissue response to SF.
Following the oral dose of SF, tissue levels of SF equivalents rapidly increased in the rats, and reached up to 280 times over the background level. Highest levels were detected at 1.5hr after dosing and SF was largely if not completely cleared from the organs at 24 hours, indicating a relatively short tissue retention time. Exposure to SF was highest in the stomach and lowest in the prostate and rectum--exposure levels decreased rapidly descending down the gastrointestinal tract. Of the genitourinary organs, bladder exposure was the highest (compared to kidney and prostate). Other organs tested, including heart, liver, lung and pancreas, had very low exposures to SF compared to that of the stomach.
However results were a little different when the researchers analysed the GST and NQO1 activities in the rat tissues after treatment with oral SF. They found that the tissue with the highest enzyme induction was the bladder and that stomach levels of GST and NQO1 were not much different from that of the duodenum and jejunum, despite having much higher exposure to SF. Induction in most of the other tissues was negligible. Overall, results show that low tissue exposure to SF is correlated to low levels of GST and NQO1 induction but that high tissue exposure does not necessarily correlate with a high response of these enzymes.
The study results overall demonstrate a high oral bioavailability for SF, and a rapid tissue clearance rate. Stomach and bladder were amongst the organs with the highest tissue levels of SF< and the bladder had the highest levels of inducible enzymes present. This suggests, in terms of chemoprevention, that the bladder may be one of the organs that benefits most from oral supplementation of SF. That said, induction of phase 2 enzymes is only one of the many chemopreventative properties of SF and further study is needed to assess the relationship between tissue exposure to SF and other chemopreventative effects of this agent.
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|Publication:||Australian Journal of Herbal Medicine|
|Date:||Sep 1, 2013|
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