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Investigated if carcinogen defense (phase 2) enzymes could be induced in the prostate …

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- Modest induction of phase 2 enzyme activity in the F-344 rat prostate

All compounds were well tolerated by the animals and there was no apparent toxicity over the duration of the study. None of the compounds affected the relative weights of the prostate, kidneys, liver or bladder after gavage feedings over 5 days. Body weights did not differ significantly between the groups fed candidate compounds and the control animals (Table 1). However, compared to initial body weights, there was an 8% decrease in body weight in the sulforaphane treated group after 5 days (P = 0.03), and non-significant increases (1–5%) in the body weights of the other 4 groups.

Sulforaphane treated animals showed significantly higher NQO1, total GST and GST-mu enzymatic activities in their prostate tissues compared to control animals (Figure 1 and Tables 2, 3 and 4) although the degree if increase was modest (1.2- to 1.8-fold). Compared to controls, β-naphthoflavone treated animals showed small, statistically significant higher levels of NQO1 activity, no differences in total GST enzymatic activity, and moderately elevated GST-mu activity in the prostate. Curcumin treated animals also displayed significantly higher total GST and GST-mu activities in prostate tissues over control levels, although, again, the differences were modest. Prostate tissues from dimethyl fumarate treated animals did not show differences in NQO1, total GST or GST-mu enzymatic activities compared to controls.

The effects of sulforaphane, β-naphthoflavone, curcumin and dimethyl fumarate on phase 2 enzyme activity in the liver, kidney and bladder in many ways paralleled that observed in the prostate. Liver tissues from animals treated with sulforaphane, β-naphthoflavone, and to a lesser extent dimethyl fumarate, showed modestly higher NQO1 enzyme activity compared control animals, while curcumin appeared to have no effect (Figure 2A and Table 2). All four compounds resulted in significantly higher total glutathione transferase enzymatic activity in the livers of treated animals compared to controls, and sulforaphane produced the greatest elevation (Figure 2B and Table 3). Somewhat paradoxically GST-mu activity levels in the liver did not differ significantly between animals treated with inducer compounds and controls and were actually lower in sulforaphane-treated animals (Table 4). NQO1 enzymatic activity was also higher in the kidney tissues of the sulforaphane, β-naphthoflavone and dimethyl fumarate treated animals compared to controls, while NQO1 enzyme activities in curcumin treated animals matched those seen in controls (Figure 2A and Table 2). On the other hand, kidney levels of total GST and GST-mu enzymatic activity were no different between the 4 inducer compound treated groups and the controls except for induction of GST-mu by curcumin (Figure 2B and Tables 3 and 4). Interestingly, NQO1 and total glutathione transferase enzymatic activities were dramatically higher in the bladder tissues of the sulforaphane treated animals compared to the controls (4.4-fold and 4.2-fold, respectively) (Figure 2A and 2B, and Tables 2 and 3). NQO1 enzyme activities in bladder tissues were also significantly increased over controls in the animals treated with β-naphthoflavone, curcumin and dimethyl fumarate, although the differences were not as marked as in the sulforaphane-treated animals. Total GST enzyme specific activities did not differ significantly from control bladder tissues for any of the three compounds.

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