Influence Of Borneolum Syntheticum On Cytochrome Enzymes In Liver Microsome

Influence of borneolum syntheticum on cytochrome enzymes in liver microsomeBorneolum syntheticum is a traditional Chinese drug, its component are borneol not less than 55.0%. It is mild cold in nature, bitter and acrid in taste, mainly acts on heart, spleen and lung meridian tropism. Its main effect is waking up the patient from unconsciousness, clearing away the heat and relieving pains.Borneolum syntheticum exerts its effect on many ways. It is effective in myocardial ischemia for blocking alpha-adrenergic receptor.Borneol syntheticum raises the pain threshold and have local analgesic property, it is germicidal effect and is used as an local antiseptic on skin. Borneol syntheticum may accelarate the growth of neuroglial cell and improve the permeability of blood-brain barrier. It may also show its antiinflammatory effect.Borneolum syntheticum is lipid-soluble and is absorbed from the gastrointestinal tract and mucosa, it passes across the blood-brain barrier easily. Borneol can be measured in rat brain after five minuets of oral administration.Drug biotransformation is carried out in the liver by a group of nonspecific enzymes located in the smooth surface microsomes of the endoplasmic reticulum.The biotransformation of drug (the foreign components) in the liver is commonly grouped into two phases. During phase I , most drugs will be transformated into inactive pharmacologically, some drugs remain unaltered, and some become more active and toxic in nature. In this phase a polar group such as hydroxyl group, carboxyl group, amino group, and sulfhydryl group is introducedinto the drug molecules. During phase II, the free or the unmasked polar group is then conjugated with glucuronate, sulfate. glycine, acetate and so on.The hepatic endoplasmic reticulum contains oxidative enzymes called mixed-function oxidases or monooxygenase. It is composed of three kinds of systems.(l)flavoprotein, (2)hemoprotein, (S)colinephosphtidyl. Essential component in the mixed-funtion oxidase system is a hemoprotein named as cytochrome P450 .The primary electron donor which is a kind of flavoprotein may calalyze the electron transfer of NADPH-P450.A drug as substrate to be metabolized inside the liver binds to oxidized cytochrome P450, then the drug in turn is reduced by NADPH-P450.Drug-reduced cytochrome P450 complex then combines with molecular oxygen,the second electron is acquired from the donor system,and the subsequent(the drug) is oxidized with regeneration of the oxidized cytochrome P450.This process is summarized as follows.RH+NADPH+H++02^ROH+NADP++H20The process of biotransformation usually inactivates or detoxifies (or both) the administered drugs or the ingested poisons,but other reactions may also take place. OBJECTIVE:To study the influence of borneolum syntheticum on the cytochrome enzymes in liver microsome.viMETHODS:Rats and mice were used for experiments.The concentration of cytochrome P450 and cytochrome bt in rat liver microme and concentration of borneol in rat serum were determined, while the effect of borneolum syntheticum on sleeping time induced by pentobarbital sodium and barbital sodium were measured in mice respectively. Frequency and interval of adiministration for borneolum syntheticum were different.Four groups(with their controls) of rats: given the oral borneolum syntheticum dosage (125mg/kgb.w):(T)once,l hour after the dose; ? doses (3 days,once/day); ?6 doses (6 days,once/day);? doses (3 days,twice/day); 24 hours after the last dose,the rat's liver was taken under 4癈 for the preparation of P450. Liver microsomes were prepared by differential centrifugation according to the method of Gibson GG. Protein concentration was determined by UV absorbtion method using boving serum albumin as a standard. Contents of cytochrome P450 and b5 in isolated microsomes were determined according to the methods of Omura and Sato.Each control group treated corn oil with the same way.For all of them, 24 hours after the last dose.given the same dose of borneo...