Fawzy Elbarbry
Pacific University, USA
Title: Modulation of drug metabolizing enzymes by dietary doses of sulforaphane; role in its antihypertensive and anti-oxidant effect in spontaneously hypertensive rats
Biography
Biography: Fawzy Elbarbry
Abstract
Aim: We have previously demonstrated that exposure of spontaneously hypertensive rats (SHR) to sulforaphane (SF) results in resisting the normal progressive rise in blood. Th is study aims to investigate the potential eff ect of these dietary doses of SF on hepatic drug metabolizing enzymes in SHR.
Methods: Rats were treated for eight weeks with 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. Th e activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase (mEH) were measured in hepatic microsomes. Cytosolic fraction was utilized to measure total glutathione (GSH) level and activity of selected antioxidant enzymes.
Results: At the high dose, SF treatment resulted in a signifi cant reduction of CYP1A2 and CYP2C9 activities that were accompanied by a parallel decline in their apoproteins. Similarly, activities of CYP2B1/2 and mEH were inhibited only by high dose SF treatment. No eff ect of SF was observed on the rest of the studied phase I enzymes. On the other hand, both low and high doses of SF resulted in a signifi cant induction of both hepatic glutathione level and activities of superoxide dismutase (SOD) and catalase. Only the high dose SF induced the activities of hepatic glutathione-S-transferases (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) to a signifi cant eff ect.
Conclusion: Th is study demonstrates that dietary doses SF has the potential to offer chemoprevention through stimulation of the endogenous antioxidants and inhibiting CYP enzymes involved in bioactivation of procarcinogens.