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Journal Article 
Activation Of Nuclear Receptors Car And Nrf2 By Garlic And Garlic Constituents 
Fisher, C; Augustine, LM; Bejati, S; Maher, J; Nelson, DM; Klaassen, CD; Lehman-Mckeeman, L; Cherrington, NJ 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
Garlic contains several linear sulfur compounds, including diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS), capable of inducing a number of drug metabolizing enzymes including cytochrome P450 (CYP) 2B and NAD(P)H quinone oxidoreductase (NQO1). CYP2B and NQO1 are induced via nuclear receptors constitutive androstane receptor (CAR) and nuclear factor E2-related factor 2 (Nrf2), respectively. The purpose of this study was to determine whether garlic oil and specific constituents activate CAR and/or Nrf2. Female Wistar Kyoto (WKY) rats express little CAR protein and exhibit significantly lower induction of CYP2B1/2 by phenobarbital than males. Garlic oil, DAS, DADS and DATS induced CYP2B1/2 mRNA levels to a greater extent in WKY males than in females, suggesting CAR activation. The 70 fold induction of CYP2B10 observed in wild type (WT) mice by DAS was attenuated in CAR-/- mice. Treatment of transiently transfected mice resulted in garlic oil and gt; DAS and gt; DATS and gt; DADS activation of the human CYP2B6 promoter in vivo. Additionally, Nrf2 activation was implicated by a 5-fold induction of NQO1 by DAS in WT mice that was completely absent in Nrf2-/- mice. These results indicate that garlic and select constituents activate not only CAR, but can also lead to the activation of Nrf2.