Mutagenic activation and detoxification of benzo[a]pyrene in vitro by hepatic cytochrome P450 1A1 and phase II enzymes in three meat-producing animals

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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NO-donating aspirin induces phase II enzymes in vitro and in vivo

Carcinogenesis ◽

10.1093/carcin/bgi262 ◽

2005 ◽

Vol 27 (4) ◽

pp. 803-810 ◽

Cited By ~ 30

Author(s):

Jianjun Gao ◽

Khosrow Kashfi ◽

Xiaoping Liu ◽

Basil Rigas

Keyword(s):

Phase Ii ◽

Phase Ii Enzymes

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Mechanism-based inhibition of Alantolactone on human cytochrome P450 3A4 in vitro and activity of hepatic cytochrome P450 in mice

Journal of Ethnopharmacology ◽

10.1016/j.jep.2015.03.061 ◽

2015 ◽

Vol 168 ◽

pp. 146-149 ◽

Cited By ~ 15

Author(s):

Chong-Zhen Qin ◽

Qiao-Li Lv ◽

Na-Yiyuan Wu ◽

Lin Cheng ◽

Yun-Chen Chu ◽

...

Keyword(s):

Cytochrome P450 ◽

Cytochrome P450 3A4 ◽

Human Cytochrome ◽

Hepatic Cytochrome

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beta-Naphthoflavone abolishes interrenal sensitivity to ACTH stimulation in rainbow trout

Journal of Endocrinology ◽

10.1677/joe.0.1570063 ◽

1998 ◽

Vol 157 (1) ◽

pp. 63-70 ◽

Cited By ~ 40

Author(s):

JM Wilson ◽

MM Vijayan ◽

CJ Kennedy ◽

GK Iwama ◽

TW Moon

Keyword(s):

Cytochrome P450 ◽

Rainbow Trout ◽

Acth Stimulation ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Treated Fish ◽

First Time ◽

Hepatic Cytochrome ◽

Stimulation Of

We report for the first time that beta-naphthoflavone (BNF) abolishes ACTH stimulation of cortisol production in rainbow trout (Oncorhynchus mykiss). There was significantly higher hepatic cytochrome P450 content and ethoxyresorufin O-de-ethylase and uridine-5'-diphosphoglucuronic acid transferase activities in BNF-treated fish than in sham-treated controls. BNF did not significantly affect either plasma turnover or tissue distribution of [3H]cortisol-derived radioactivity. Hepatic membrane fluidity and hepatocyte capacity for cortisol uptake were not altered by BNF as compared with the sham-treated fish. These results taken together suggest that BNF does not affect cortisol-clearance mechanisms in trout. A 3 min handling disturbance period elicited a plasma cortisol response in the sham-treated fish; however, the response in the BNF-treated fish was muted and significantly lower than in the sham fish. This in vivo response corroborates the lack of interrenal sensitivity to ACTH in vitro in the BNF-treated fish, suggesting that BNF affects the ACTH pathway in trout. Our results suggest the possibility that cytochrome P450-inducing compounds may affect cortisol dynamics by decreasing interrenal responsiveness to ACTH stimulation in fish, thereby impairing the physiological responses that are necessary for the animal to cope with the stressor.

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