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We previously demonstrated that  Peganum harmala  L. extract and its main active constituents, harmine and harmaline inhibit the 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD)-mediated induction of the carcinogen-activating enzyme, Cyp1a1,  in vitro . However, the effect of both alkaloids on Cyp1a1  in vivo  has not been investigated. Therefore, the aim of this study is to examine the effect of harmine and harmaline on TCDD-mediated induction of Cyp1a1 in mice livers and lungs. C57BL/6 male mice were distributed into four groups ( n  = 6). First group received vehicle, while the second group received TCDD (i.p.). The third and fourth groups received either harmine or harmaline (i.p.) × 3 times along with TCDD one time with the mid dose of harmine and harmaline. All mice were sacrificed after 14 h from TCDD injection, and livers and lungs were isolated. The effect of harmine and harmaline on TCDD-mediated induction of Cyp1a1 mRNA, protein, and activity levels was determined using real-time PCR, Western blot analysis, and 7-ethoxyresurofin as a substrate, respectively. Our results showed that harmine and harmaline significantly decreased the TCDD-mediated induction of Cyp1a1 in both the livers and lungs. We concluded that harmine and harmaline are promising candidate to inhibit TCDD-mediated induction of Cyp1a1 in mice hepatic and extrahepatic tissues.

Harmine and Harmaline Downregulate TCDD-Induced Cyp1a1 in the Livers and Lungs of C57BL/6 Mice