ABSTRACT
Aim To evaluate the mucosal-protective effects of carboxymethylpachyman( CMP) on Fluorou-racil(5-Fu)-induced mice intestinal mucositis and ex-plore its mechanisms. Methods ICR mice were as-signed randomly to four groups:normal group( n=8;re-ceiving pure water orally for 14 d) ,CMP group( n=8;200 mg·kg-1 CMP for 14 d orally),5-Fu group(n=8;25 mg·kg-1 5-Fu for 7 d,intraperitoneally( i. p. ) , and CMP+5-Fu group( n=8;200 mg·kg-1 CMP for 14 d orally and 25 mg·kg-1 5-Fu for 7 d,i. p. ). At day 14the mice were sacrificed. The intestinal propel-ling rate and the colon length were measured. ROS, GSH and IL-1βcontents,and CAT,GSH-Px activities in homogenate supernatant of PPs were measured by kits for observing the effects of CMP on mice lipid peroxida-tion and intestinal mucosal inflammatory induced by 5-Fu. Colon tissues were used for hematoxylin and eosin ( HE ) staining for the determination of the effect of CMP on mice colon histopathology, immunohistochem-istry for the protein levels of NF-κB and p-p38 . Results CMP significantly extended colon lengths,accelerate the intestinal propelling rates, reduced colonic mucosa epithelium goblet cell loss, inflammatory cells infiltra-tion,and crypt depth shallow induced by 5-Fu. CMP obviously reduced ROS and IL-1β contents, and pre-vented reductions in homogenate supernatant of PPs GSH content, CATand GSH-Px activities by 5-Fu ad-ministration,and also reduced the expression of NF-κB and p-p38 in colon tissues. However, CMP alone had no effect on the colon of normal mice. Conclusion The current study demonstrates that CMP may have sig-nificant protective effects against 5-Fu-induced intesti-nal mucositis. Its mechanism may be related to enhan-cing the antioxidant activity,anti-inflammatory and an-ti-apoptotic effects.
ABSTRACT
AIM: To establish a sensitive method for quantitative determination of astragaloside Ⅳ (AGS-Ⅳ) in plasma and a preliminary evaluation of its pharmacokinetics parameters in intact rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was applied for determining AGS-Ⅳ in plasma by using digoxin as the internal standard (I.S.). Six rats were given AGS-Ⅳ 2.0 mg/kg by intravenous infusion for 5 min. Blood samples were drawn intermittently with each intact rat from left femoral artery at 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4, 6, 10, 14 and 24 h after medication. The samples were prepared by solid phase extraction and analyzed through a triple quadrupole mass spectrometer equipped with an electrospary probe. The samples were monitored in selected ion recording (SIR) mode of positive ions by using target ions at m/z 807.5 for AS- Ⅳand at m/z 803.5 for I.S. RESULTS: Calibration curves were linear over the ranges 1-1 000 ng/mL for AGS-Ⅳ (r=0.9992). The intra-and inter-day assay variability values were less than 6% and 8%, respectively. Extraction recoveries from plasma were 92.8%-98.4% for AGS-Ⅳ and 80.0%-90.9% for digoxin, respectively. The lower limit of quantitation (LLOQ) for AGS-Ⅳ was 0.5 ng/mL. The concentration-time curves of AGS-Ⅳ for each rat were fitted to an open two-compartment model by CAPP program. The pharmacokinetics parameters of AGS-Ⅳ were as following: the elimination half-life (t1/2β), clearance rate (CL), distribution volume at steady state (Vss), and AUC0-∞ were (3.46±0.52) h, (0.47±0.02) L/h, (0.76±0.16) L/kg and (4.27±0.19) μg·mL-1·h, respectively. CONCLUSION: These results show that this method is satisfied for the measurements of pharmacokinetics study for AGS-Ⅳ.