1.Relationship etween Electroacupuncture and Spleen Function on Leukocyte
Pinglong SUN ; Yubao ZHOU ; Huijuan MAO ; Huihui WU ; Linglin BU ; Jia SUN ; Hengyan GUO
Journal of Acupuncture and Tuina Science 2007;5(6):336-340
Objective: To explore the underlying mechanism by which acupuncture regulates the peripheral leukocyte count and observe the relationship between the effects of electroacupuncture (EA) and the spleen ultrastructure in leukopenia. Methods: Leukopenia models of rabbits were established by injecting cyclophosphamide (CY) into rabbits' ear vein,and then the rabbits were treated with acupuncture. The peripheral leukocyte count and classification were measured daily. At last, after the animals were anesthesized, the abdominal cavity was opened, and a piece of spleen tissue was cut. The diameter of splenic sinusoid basal lamina eyehole was measured under electric microscope. Results: The peripheral blood leukocyte count in the EA group increased significantly with shift to right of the granulocyte nuclei compared with model control group (P<0.01). Moreover, the calibers of splenic sinusoid basal lamina eyehole in the EA group were larger than those in the model control group (P<0.05). Conclusion: Acupuncture can enhance the peripheral leukocyte count by promoting spleen activity in the early phase of leukopenia.
2.Comparison of the inhibition potentials of icotinib and erlotinib against human UDP-glucuronosyltransferase 1A1.
Xuewei CHENG ; Xia LV ; Hengyan QU ; Dandan LI ; Mengmeng HU ; Wenzhi GUO ; Guangbo GE ; Ruihua DONG
Acta Pharmaceutica Sinica B 2017;7(6):657-664
UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug-drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risksUGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The ICvalues of icotinib and erlotinib against UGT1A1-mediated NCHN--glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with thevalues of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risksUGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration-time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risksUGT1A1 inhibition.