Z H Liu

Zhejiang University, Hangzhou, Zhejiang Sheng, China

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Publications (2)5.65 Total impact

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    ABSTRACT: Ginkgolic acids have been shown to possess allergenic as well as genotoxic and cytotoxic properties. The question arises whether the metabolism of ginkgolic acids in the liver could decrease or increase their toxicity. In this study, the in vitro metabolism of ginkgolic acid (15:1, GA), one component of ginkgo acids, was investigated as a model compound in Sprague-Dawley rat liver microsomes. The metabolites were analyzed by ultra-performance liquid chromatography coupled with photodiode array detector/negative-ion electrospray ionization tandem mass spectrometry (UPLC-PDA/ESI-MS/MS) and hydrogen/deuterium (H/D) exchange. The result showed that the benzene ring remained unchanged and the oxidations occurred at the side alkyl chain in rat liver microsomes. At least eight metabolites were found. Among them, six phase I metabolites were tentatively identified. This study might be useful for the investigation of toxicological mechanism of ginkgolic acids.
    Rapid Communications in Mass Spectrometry 08/2009; 23(13):1899-906. · 2.51 Impact Factor
  • Z H Liu, S Zeng
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    ABSTRACT: Ginkgolic acids and related alkylphenols (e.g. cardanols and cardols) have been recognized as hazardous compounds with suspected cytotoxic, allergenic, mutagenic and carcinogenic properties. To determine whether the phase I metabolism could contribute to their cytotoxicity, we investigated the cytotoxicity of one model compound, ginkgolic acid (15:1), using in vitro bioassay systems. In the first step, cytochrome P450 enzymes involved in ginkgolic acid metabolism were investigated in rat liver microsomes; then, two in vitro cell-based assay systems, primary rat hepatocytes and HepG2 cells, were used to study and the measurement of MTT reduction was used to assess cell viability. Results indicated that the cytotoxicity of ginkgolic acid in primary rat hepatocytes was lower than in HepG2 cells. Ginkgolic acid was demonstrated less cytotoxicity in four-day-cultured primary rat hepatocytes than in 20-h cultured ones. Co-incubation with selective CYP inhibitors, alpha-naphthoflavone and ketoconazole, could decrease the cytotoxicity of ginkgolic acid in primary rat hepatocytes. In agreement, pretreatment with selective CYP inducers, beta-naphthoflavone and rifampin, could increase the cytotoxicity of ginkgolic acid in HepG2 cells. These findings suggest that HepG2 cells were more sensitive to the cytotoxicity of ginkgolic acid than primary rat hepatocytes, and CYP1A and CYP3A could metabolize ginkgolic acid to more toxic compounds.
    Toxicology Letters 07/2009; 187(3):131-6. · 3.15 Impact Factor

Publication Stats

18 Citations
5.65 Total Impact Points

Institutions

  • 2009
    • Zhejiang University
      • College of Pharmaceutical Sciences
      Hangzhou, Zhejiang Sheng, China