Polymorphism of phase II enzymes: identification of new enzymes and polymorphic variants by database analysis

Abstract Objectives The aim of this research was to evaluate the chemopreventive activity of Moringa oleifera(MO) leaves in a colitis-associated colon carcinogenesis model. Our hypothesis was that moringa leaves contain bioactive compounds capable of inducing antioxidant systems, reducing the incidence of colonic lesions, as well as modulating the expression of genes involved in the inflammatory response and carcinogenesis. Methods Forty male (CD-1) mice were divided into 5 groups (n = 8). G1: Healthy control; G2: Positive control induced with azoxymethane (AOM, 10 mg/Kg body weight, intraperitoneal injection) and three cycles of dextran sulfate sodium (DSS, 1.5% in drinking water); groups G3, G4, G5 were induced with AOM/DSS and supplemented with 5, 10 and 20% of MO, respectively. Morphological and histopathological parameters, induction of glutathione-S-transferase (GST) and quinone reductase (QNO1), lipid peroxidation, myeloperoxidase (MPO) activity, short chain fatty acids (SCFA) production and the expression of genes related to cancer-inflammation were evaluated. Results Significant differences (p < 0.05) were found for the groups supplemented with 5, 10 and 20% of MO in morphological and histopathological parameters compared to positive control. Regarding the induction of enzymes, GST and QNO1 had an increase up to 2.5 times in the liver and 2.1 times in the colon in groups supplemented with 20% MO (GST > QNO1). A decrease in MPO activity (∼50%), and lipid peroxidation (1.5–2.3 times) were found in groups with 10 and 20% of MO compared to the positive control. All the groups supplemented with MO showed an increase in SCFAs production. G3, G4 exhibited an increase (up to 0.5–0.7 times) in the production of acetic acid, and G5 showed a significant increase (∼3 times) in butyric and propionic acid compared to the positive control (p < 0.05). Conclusions The results of this study provide in vivo evidence that MO attenuates the colitis-associated colon cancer in mice through the induction of antioxidant and phase II enzymes as well as the decrease of biomarkers of oxidative stress in the liver and colon. Funding Sources This study was supported by Universidad Autónoma de Querétaro (FOFI project) and the University of Illinois at Urbana-Champaign.

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Effect of phytochemicals on phase II enzyme expression in infant human primary skin fibroblast cells

British Journal Of Nutrition ◽

10.1017/s0007114512000554 ◽

2012 ◽

Vol 108 (12) ◽

pp. 2158-2165 ◽

Cited By ~ 8

Author(s):

Eliz Warwick ◽

Aedín Cassidy ◽

Bryan Hanley ◽

Zeina E. Jouni ◽

Yongping Bao

Keyword(s):

Phase Ii ◽

Developmental Stages ◽

Later Life ◽

Phase Ii Enzymes ◽

Protein Levels ◽

Metabolic Plasticity ◽

Mrna Induction ◽

Age Related ◽

Adult Cell

Phase II metabolising enzymes enable the metabolism and excretion of potentially harmful substances in adults, but to date it is unclear whether dietary phytochemicals can induce phase II enzymes differently between adults and infants. We investigated the expression of phase II enzymes in an in vitro model of primary skin fibroblasts at three different developmental stages, 1 month, 2 years and adult, to examine potential differences in age-related phase II enzymes in response to different phytochemicals (5–20 μm) including sulphoraphane, quercetin and catechin. Following phytochemical treatment, a significant increase in mRNA of glutathione S-transferase A1 (GSTA1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) was observed, with the most marked increases seen in response to sulphoraphane (3–10-fold for GSTA1, P = 0·001, and 6–35-fold for NQO1, P = 0·001–0·017). Catechin also induced 3–5-fold changes in NQO1 transcription, whereas quercetin had less effect on NQO1 mRNA induction in infant cells. Moreover, NQO1 protein levels were significantly increased in 2-year-old and adult cell models in response to sulphoraphane treatment. These results suggest that metabolic plasticity and response to xenobiotics may be different in infants and adults; and therefore the inclusion of phytochemicals in the infant diet may modulate their induction of phase II metabolism, thereby providing increased protection from potentially harmful xenobiotics in later life.

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