Modulation of Kupffer cells on hepatic drug metabolism

AIM: To observe the effects of Kupffer cells on hepatic drug metabolic enzymes.METHODS: Kunming mice were ip injected with GdCI310,20, 40 mg/kg to decrease the number and block the function of kupffer cells selectively. The contents of drug metabolic enzymes, cytochrome 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 microsome and S9-GSTpi, S9-GST in supernatant of 9 000 g were accessed 1 d after the injection. The time course of alteration of drug metabolic enzymes was observed on d 1, 3, and 6 treated with a single dose GdCI3. Mice were treated with Ange/ica sinensis polysaccharides (ASP) of 30, 60, 120 mg/kg, ig, qd x6 d, respectively and the same assays were performed.RESULTS: P450 content and NADPH-C, ANH, AMD, and EMD activities were obviously reduced 1 d after Kupffer cell blockade. However, mGST and S9-GST activities were significantly increased. But no relationship was observed between GdCI3 dosage and enzyme activities. With single dose GdCI3 treatment, P450 content, NADPH-C, and ANH activities were further decreased following Kupffer cell blockade lasted for 6 d, by 35.7%, 50.3%, 36.5% after 3 d, and 57.9%, 57.9%, 63.2% after 6 d, respectively. On the contrary, AMD, EMD, mGST, and S9-GST activities were raised by 36.5%, 71.9%, 23.1%, 35.7% after 3 d,and 155%, 182%, 21.5%, 33.7% after 6 d, respectively.Furthermore, the activities of drug metabolic enzymes were markedly increased after 30 mg/kg ASP treatment,and decreased significantly after 120 mg/kg ASP treatment.No change in activity of S9-GSTpi was observed in the present study.CONCLUSION: Kupffer cells play an important role in the modulation of drug metabolic enzymes. The changes of drug metabolic enzyme activities depend on the time of kupffer cell blockade and on the degree of Kupffer cells activated. A low concentration of ASP increases the activities of drug metabolic enzymes, but a high concentration of ASP decreases the activities of drug metabolic enzymes.

AIM:To observe the effects of Kupffer cells on hepatic drug metabolic enzymes. METHODS:Kunming mice were ip injected with GdCl_310, 20,40mg/kg to decrease the number and block the function of kupffer cells selectively.The contents of drug metabolic enzymes,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 microsome and S9-GSTpi,S9-GST in supernatant of 9000g were accessed 1d after the injection.The time course of alteration of drug metabolic enzymes was observed on d 1,3,and 6 treated with a single dose GdCl_3.Mice were treated with Angelica sinensis polysaccharides (ASP) of 30,60,120mg/kg,ig,qd×6d,respectively and the same assays were performed. RESULTS:P450 content and NADPH-C,ANH,AMD,and EMD activities were obviously reduced 1d after Kupffer cell blockade.However,mGST and S9-GST activities were significantly increased.But no relationship was observed between GdCl_3 dosage and enzyme activities.With single dose GdCl_3 treatment,P450 content,NADPH-C,and ANH activities were further decreased following Kupffer cell blockade lasted for 6d,by 35.7%,50.3%,36.5% after 3d,and 57.9%,57.9%,63.2% after 6d,respectively.On the contrary,AMD,EMD,mGST,and S9-GST activities were 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 enzymes were 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 the present study. CONCLUSION:Kupffer cells play an important role in the modulation of drug metabolic enzymes.The changes of drug metabolic enzyme activities depend on the time of kupffer cell blockade and on the degree of Kupffer cells activated.A low concentration of ASP increases the activities of drug metabolic enzymes,but a high concentration of ASP decreases the activities of drug metabolic enzymes.