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Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice
John D Clarke1, Anna Hsu, David E Williams
1Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon 97331, USA.
Purpose:
To determine the metabolism and tissue distribution of the dietary chemoprotective agent sulforaphane following oral administration to wild-type and Nrf2 knockout (Nrf2(-/-)) mice.
Methods:
Male and female wild-type and Nrf2(-/-) mice were given sulforaphane (5 or 20 micromoles) by oral gavage; plasma, liver, kidney, small intestine, colon, lung, brain and prostate were collected at 2, 6 and 24 h (h). The five major metabolites of sulforaphane were measured in tissues by high performance liquid chromatography coupled with tandem mass spectrometry.
Results:
Sulforaphane metabolites were detected in all tissues at 2 and 6 h post gavage, with the highest concentrations in the small intestine, prostate, kidney and lung. A dose-dependent increase in sulforaphane concentrations was observed in all tissues except prostate. At 5 micromole, Nrf2(-/-) genotype had no effect on sulforaphane metabolism. Only Nrf2(-/-) females given 20 micromoles sulforaphane for 6 h exhibited a marked increase in tissue sulforaphane metabolite concentrations. The relative abundance of each metabolite was not strikingly different between genders and genotypes.
Conclusions:
Sulforaphane is metabolized and reaches target tissues in wild-type and Nrf2(-/-) mice. These data provide further evidence that sulforaphane is bioavailable and may be an effective dietary chemoprevention agent for several tissue sites.
Insights
Sulforaphane, a dietary chemoprotective agent, is metabolized and distributed to various tissues in mice. It shows bioavailability, suggesting potential as a chemoprevention agent.
Area of Science:
- Nutritional biochemistry
- Pharmacokinetics
- Cancer chemoprevention
Background:
- Sulforaphane is a natural compound found in cruciferous vegetables.
- It is recognized for its potential chemoprotective and anti-cancer properties.
- Understanding its metabolism and distribution is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the metabolism and tissue distribution of sulforaphane.
- To compare sulforaphane's pharmacokinetics in wild-type and Nrf2 knockout mice.
- To assess the influence of Nrf2 genotype and dose on sulforaphane bioavailability.
Main Methods:
- Oral administration of sulforaphane (5 or 20 micromoles) to male and female wild-type and Nrf2 knockout mice.
- Collection of plasma and various tissues (liver, kidney, intestine, etc.) at 2, 6, and 24 hours post-administration.
- Quantification of sulforaphane metabolites using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).
Main Results:
- Sulforaphane metabolites were detected in all tested tissues within 2-6 hours, with high concentrations in the small intestine, prostate, kidney, and lung.
- A dose-dependent increase in sulforaphane levels was observed in most tissues.
- Nrf2 knockout mice showed no significant difference in sulforaphane metabolism at a low dose (5 micromoles), but Nrf2 knockout females given a high dose (20 micromoles) exhibited increased tissue concentrations.
Conclusions:
- Sulforaphane is effectively metabolized and distributed to target tissues in both wild-type and Nrf2 knockout mouse models.
- The study confirms the bioavailability of sulforaphane following oral administration.
- These findings support the potential of sulforaphane as a dietary chemoprevention agent for various tissues.
