ABSTRACT
OBJECTIVE: To compare the effect on CYP450 isoenzyme in rats with acute liver injury induced by different chemicals. METHODS: Acute liver injury model of rats induced by tetrachloromethane(CCl4), D-aminogalactose(D-GalN)/lipopolysaccharide(LPS), α-naphthyl isothiocyanate(ANIT) respectively whereas the normal Wistar rats were used as controls. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the blood samples were collected from the fundus venous plexus of rat at different time point, the blood drug concentration of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK Solutions 2™. Compared with normal rats, the changes of the probe drug pharmacokinetics in different rat models were used as the basis for the evaluation of the metabolic activity of CYP450 isoenzyme. RESULTS: Compared with normal rats, the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 of CCl4 group rats were significantly inhibited, and the activities of CYP3A4 was slightly inhibited; the activities of CYP2C9, CYP2D6 and CYP3A4 of D-GalN/LPS group rats were significantly induced, and the activity of CYP2D6 and CYP3A4 was slightly induced, and the activity of CYP1A2 was not significantly affected, but the activity of CYP2C19 was significantly inhibited; the activities of CYP2C9, CYP2C19 and CYP3A4 of ANIT group rats were significantly induced, the activity of CYP3A4 were slightly induced, and the activity of CYP2D6 was not significantly affected, but the activity of CYP1A2 was significantly inhibited. CONCLUSION: There are significant differences in the activities of CYP450 isoenzyme in the rat model of acute liver injury induced by different chemicals.
ABSTRACT
To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.
Subject(s)
Animals , Humans , Male , Rats , Cytochrome P-450 Enzyme System , Genetics , Metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Chemistry , Pharmacokinetics , Isoenzymes , Genetics , Metabolism , Liver Cirrhosis , Drug Therapy , Genetics , Mass Spectrometry , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical value of retrospective electrocardiogram (ECG) -editing technique in dual-source computed tomography (CT) coronary angiography in patients with arrhythmia.</p><p><b>METHODS</b>Totally 73 patients with arrhythmia during dual-source CT coronary angiography were included into this study. A retrospective gating technique and ECG-editing technique (Insert Sync; Disable Sync; Delete Sync; Shift R-peak) were used in patients who needed ECG-editing. Two experienced radiologists evaluated in consensus all pre-editing and post-editing reconstructed images and recorded scores according to the American Heart Association guidelines on coronary segmentation on a per segment basis. Image quality of all coronary segments was assessed using a four-point grading scale from excellent (4 scores) to non-assessable (1 score) .</p><p><b>RESULTS</b>The overall mean image quality of 34 patients who did not need ECG-editing was 3.42 ± 0.20. In 39 patients who needed ECG-editing, the overall mean image quality before and after ECG-editing was 2.39?0.37 and 3.22?0.24. The mean image quality in every segment between pre-editing and post-editing was also significantly different (P<0.01) .</p><p><b>CONCLUSION</b>ECG-editing technique can remarkably improve image quality of coronary artery segments by reducing or even eliminating the artifact produced by arrhythmia during dual-source CT coronary angiography.</p>