DOI: 10.5176/2345-783X_PHARMA15.41
Authors: Fawzy Elbarbry, Anik Amin and Margarita Can
Abstract:
We have previously demonstrated that exposure of Spontaneously Hypertensive Rats (SHR) to dietary doses of Sulforaphane results in resisting the progressive rise in blood pressure that is normally seen in this rat model in a dose-dependent manner. The principal objective of the current study was to investigate the potential effect of these dietary doses of SF on drug metabolizing enzymes in SHR Methods: Rats were treated for 8 weeks with either drinking water alone (control) or SF (20 or 40 mg/kg) added to drinking water. At the end of treatment rats were euthanized, followed by preparation of liver microsomes and cytosols. The activity of the following cytochrome P45 (CYP) enzymes were measured in hepatic microsomes using specific probe substrates; CYP1A1, CYP1A2, CYP2B1/2, CYP2C9, CYP2E1, and CYP3A4. Cytosolic fraction was utilized to measure total glutathione (GSH) level and activity of the following antioxidant enzymes; GSH-reductase (GR), GSH-peroxidase (GPx), GSH-S Transferases (GST), Superoxide dismutase (SOD), and Catalase. Results: At the high dose, SF treatment resulted in a significant inhibition of CYP1A2 (measured as dealkylation of methoxyresorufin) and CYP2B1/2 (measured as dealkylation of pentoxyresorufin) activities. No effect of SF was observed on the rest of the studied CYP enzymes. On the other hand, both low and high doses of SF resulted in a significant induction of both hepatic glutathione level and activities of SOD and Catalase. Only the high dose SF induced the activities of hepatic GST, GR, and GPx to a significant effect. Conclusion: This study demonstrates that SF, at dietary doses, has the potential to offer chemoprevention through stimulating the endogenous antioxidant systems and inhibiting CYP enzymes involved in bioactivation of procarcinogens. Additionally, stimulation of the impaired antioxidant system in SHR may explain the blood pressure lowering effect of SF in this rat model.
Keywords: Sulforaphane; Cytochrome P450 enzymes; Antioxidants; Glutathione; SHR
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