The Effect Of Cytochrome P-450Inducers & Inhibitors On The Biotransformation Of Certain Hormones In Rats

Drug metabolism is the main process responsible for biotransformation of xenobiotics (foreign compounds) to more water soluble compound to be easily excreted from the body. These biotransformation reactions of xenobiotics are catalyzed predominately by the CYP-450 (Cytochrome P-450) enzymes. The CYP-450 enzyme system consists of a superfamily of hemoproteins that catalyzes the oxidative metabolism of a wide variety of exogenous chemicals including drugs, carcinogens, toxins and endogenous compounds such as steroids, fatty acids and prostaglandins. Many drugs may interact with these enzymes resulting in either induction or inhibition of its metabolizing action. In the present study, we tried to investigate the effect of some CYP-450 enzymes inducer (phenytoin) and inhibitors (cimetidine and nifedipine) on metabolism of some endogenous steroidal hormone (cortisol, estrogen and progesterone), in both male and female rats. This aim was achieved through the determination of the serum level of the investigated hormones and the determination of some related parameters e.g., serum glulcose level, serum cholesterol level and some serum electrolytes level such as calcium ion and potassium ion. The present study also investigated the drug interaction between these hormones when exogenously administered concomitantly with the used inducer and inhibitors. Moreover, the present study investigated the effect of sex difference on CYP-450 induction and inhibition