Modulation of Kupffer cells on hepatic drug metabolism

AIM:To observe the effects of Kupffer cells on hepaticdrug metabolic enzymes.METHODS:Kunming mice were ip injected with GdCl_310,20,40mg/kg to decrease the number and block the functionof kupffer cells selectively.The contents of drug metabolicenzymes,cytochrorne P450,NADPH-cytochrom C redutase(NADPH-C),aniline hydroxylase (ANH),aminopyrine N-demethylase (AMD),erythromycin N-demethylase (EMD),and glutathione s-transferase (mGST) in hepatic microsomeand S9-GSTpi,S9-GST in supernatant of 9000g wereaccessed 1d after the injection.The time course ofalteration of drug metabolic enzymes was observed on d1,3,and 6 treated with a single dose GdCl_3.Mice weretreated with Angelica sinensis polysaccharides (ASP) of30,60,120mg/kg,ig,qd×6d,respectively and the sameassays were performed.RESULTS:P450 content and NADPH-C,ANH,AMD,andEMD activities were obviously reduced 1d after Kupffercell blockade.However,mGST and S9-GST activities weresignificantly increased.But no relationship was observedbetween GdCl_3 dosage and enzyme activities.With singledose GdCl_3 treatment,P450 content,NADPH-C,and ANHactivities were further decreased following Kupffer cellblockade lasted for 6d,by 35.7%,50.3%,36.5% after3d,and 57.9%,57.9%,63.2% after 6d,respectively.Onthe contrary,AMD,EMD,mGST,and S9-GST activitieswere raised by 36.5%,71.9%,23.1%,35.7% after 3d,and 155%,182%,21.5%,33.7% after 6d,respectively.Furthermore,the activities of drug metabolic enzymeswere markedly increased after 30mg/kg ASP treatment,and decreased significantly after 120mg/kg ASP treatment.No change in activity of S9-GSTpi was observed in thepresent study.CONCLUSION:Kupffer cells play an important role in themodulation of drug metabolic enzymes.The changes ofdrug metabolic enzyme activities depend on the time ofkupffer cell blockade and on the degree of Kupffer cellsactivated.A low concentration of ASP increases the activitiesof drug metabolic enzymes,but a high concentration ofASP decreases the activities of drug metabolic enzymes.