# The Impact of Sulforapahane on Sex-Specific Conditions and Hormone Balance: A Comprehensive Review
## 3 Sulforaphane
### Kear1-Nrf2 Mediation of the Antioxidant and Detoxification Effects of SF  
This now classic pathway is widely known for its upregulation of antioxidant and detoxification mechanisms, which also results in the inhibition of inflammation. Sulforaphane (SF) is recognized as the most potent naturally occurring inducer of the Kear1/Nrf2 pathway. Early work focused primarily on sulforaphane's ability to induce antioxidant and cytoprotective pathways, including those involved in the synthesis of glutathione (GSH), drug metabolism and transport, metabolic (energetics) enzymes, heme and iron metabolism, and a variety of transcription factors [37, 38, 39]. As such, we now have a much greater understanding of the role that the Kear1/Nrf2 pathway plays in immune function, mitochondrial health, and neurodevelopmental and neurodegenerative conditions.  
Glutathione is the body's most abundant endogenous antioxidant and is essential for maintaining cellular health and defense. It alternates between two states: reduced (GSH) which carries out antioxidant and detoxification functions, and oxidized (GSSG), which forms after these critical processes. Extensive evidence supports this vital role, one that maintains a balance by both inducing production of GSH and promoting the synthesis of enzymes that recycle GSSG back to its active, GSH state [40].  
Early work by [PERSON]'s group at the Cullman Chemoprotection Center at Johns Hopkins School of Medicine identified NAD(P)H quinone dehydrogenase 1 (also referred to as NAD(P)H:quinone oxidoreductase 1, NQO1, or quinone reductase in the older scientific literature) as a key and highly responsive Phase 2 enzyme, the measurement of which has been a reliable and highly predictive indicator of the cytoprotective potential of both natural and synthetic compounds. Recently, expression of NQO1 in peripheral blood mononuclear cells has been used as a proxy for the expression of the whole suite of Nrf2/Kear1 regulated protective enzymes in human clinical studies [41]. NQO1 has critical cellular antioxidant activity, directly scavenging the superoxide radical, for example, as well as exerting indirect antioxidant effects, regenerating the antioxidants GSH, CoenzymeQ10, and alpha-tocopherol, all of which play critical roles in neuroprotection, together contributing to the maintenance of the redox balance of the brain and central nervous system. In addition to its enzymatic activities, NQO1 is involved in the recognition, repair, and removal of damaged proteins. NQO1 plays a protective role against the genotoxicity of the procarcinogen benzene and its benzoquinone metabolites. SF increases NQO1 gene and protein expression through the Nrf2 signaling pathway in most tissues examined, including within the CNS [42].  
In reviewing the effects of SF on female and male health, it is helpful to attempt to separate \"normal\" age-related symptoms or issues experienced by each gender from what are clearly diseases (Table 1) and to examine the effects of SF, if any, in both prevention and treatment.  
The roles of SF in supporting healthy metabolism are extremely diverse and far-reaching, exceeding the scope of this review. However, certain effects which relate to sex-specific and primarily hormone-mediated conditions will be discussed in subsequent sections. For example: (a) the potent cytoprotective and detoxication functions of SF aid in ameliorating the effects of liver damage (e.g., NAFLD and NASH) and bolstering detoxification in healthy livers. These pathways are critical for estrogen metabolism. (b) SF offsets tissue damage due to type 2 diabetes (T2D) and aging, for example. (c) SF can directly inhibit cancer initiation, tumor cell growth, and perhaps metastasis and angiogenesis, which supports tumor expansion. Hormonal balance is intimately linked with the cancers that are uniquely prevalent in either females or males. (d) SF aids in the neutralization of xenoestrogens via various detoxification modalities.