The metabolism and hepatotoxicity of ginkgolic acid (17 : 1) in vitro / 中国天然药物

Pharmacological activities and adverse side effects of ginkgolic acids (GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA (17 : 1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA (17 : 1) in phase I and II metabolisms. The drug-metabolizing enzymes involved in GA (17 : 1) metabolism were human CYP1A2, CYP3A4, UGT1A6, UGT1A9, and UGT2B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA (17 : 1) in HepG2 cells occurred in a time- and dose-dependent manner. Further investigation showed that GA (17 : 1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1A- and CYP3A-mediated metabolism.

The metabolism and hepatotoxicity of ginkgolic acid (17 : 1) in vitro / 中国天然药物

Pharmacological activities and adverse side effects of ginkgolic acids (GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA (17 : 1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA (17 : 1) in phase I and II metabolisms. The drug-metabolizing enzymes involved in GA (17 : 1) metabolism were human CYP1A2, CYP3A4, UGT1A6, UGT1A9, and UGT2B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA (17 : 1) in HepG2 cells occurred in a time- and dose-dependent manner. Further investigation showed that GA (17 : 1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1A- and CYP3A-mediated metabolism.

Mechanism for ginkgolic acid (15 : 1)-induced MDCK cell necrosis: Mitochondria and lysosomes damages and cell cycle arrest / 中国天然药物

Ginkgolic acids (GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA (15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA (15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA (15 : 1) on MDCK cells displayed a time- and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA (15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential (ΔΨm). In propidium iodide (PI) staining analysis, GA (15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA (15 : 1) induced renal toxicity.

Establishment of reverse-phase high-performance liquid chromatography with chiral reagent derivatization for separation of fexofenadine enantiomers / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish a precolumn chiral derivatization method for determination of fexofenadine enantiomers, a chiral substrate of OATP1B1, in cellular model.</p><p><b>METHODS</b>R-(+)-phenylethyl isocyanate was selected as chiral derivatization reagent, which was reacted with fexofenadine to form carbamate derivatives. Enantiomers were identified by LC/MS and separated by RP-HPLC.</p><p><b>RESULTS</b>Under the experimental conditions, the fexofenadine enantiomers were separated completely. The standard curve was linear over the concentration range of 25-100 ng/ml (R(2)=0.9992, 0.9989). Accuracy was 101.1% and 98.3%, intra-precision was 2.4% and 3.1%, inter-precision was 3.1% and 4.0% for D1 and D2, respectively.</p><p><b>CONCLUSION</b>The method established is sensitive and accurate for determination of fexofenadine enantiomers in cells.</p>

Prevalence of occult hepatitis B virus infection and its phylogenetic features among mother-teenager pairs / 中华流行病学杂志

Objective Prevalence of occult hepatitis B virus (HBV) infection (OBI) was investigated in a paired mother-teenager population and HBV S gene variation including overt and occult HBV,was determined.Methods A follow-up study based on an initial survey of 135 mother-teenager pairs was carried out through collection of questionnaires and blood samples HBsAg were detected by ELISA method,viral load by PCR amplification and HBV S gene by phylogenetic analysis.Results 102 pairs of subjects were followed-up.Blood samples from 94 mothers and 101children were collected.OBI prevalence in mothers was 10.0％ (6/60),significantly higher than 2.0％(2/101) in teenagers.Medians of viral load were 399.9 IU/ml and 247.6 IU/ml in overt and occult HBV strains,but without significant difference.1 occult HBV strain belonged to genotype B with serotype adw while the other 7 were genotype C with serotype adr.15 of the overt HBV strains belonged to genotype B with serotype adw and the other 8 were genotype C with serotype adr.Proportions of genotype-C strains were significantly higher in occult HBV strains than in overt HBV strains.Conclusion OBI was seen in teenage-mother population.