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Establishment And Application Of Aging Model Induced By Oxidative Damage In Vivo And In Vitro, And Pharmacokinetics Of Geldanamycin In Beagle Dogs

Posted on:2007-12-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:C L ChengFull Text:PDF
GTID:1104360185468567Subject:Microbial and Biochemical Pharmacy
Abstract/Summary:PDF Full Text Request
Studies on mechanisms of aging are the hotspot of life science, and the most studies are based on the aging model system. Usually, the aging model system includes the cell model and the model biology such as saccharomyces cerevisiae, c. elegans, drosphila melanogaster so on. Cell model is the important model in aging research, since the cell is the ultimate unit of life and there are many correlations between cellular senescence and aging.Free radical (FR) and reactive oxygen species (ROS) accumulate as aging processed both in cell and in tissue. The increased FR and ROS cause damage to the macromolecules including proteins, nucleonic acid etc, leading to aging eventually. The study on the mechanism of aging, and establishment of aging model is important for searching and screening anti-aging drugs.Cellular senescence is a program activated by normal in response to various types of stress including telomere uncapping, DNA damage, oxidative stress, oncogene activity and so on, also termed "prematuresenescence"Thus, the cellular senescence model was established with H202 and screened for anti-aging drugs from natural products compounds. Also, we explored the mechanism of cellular senescence model and established mice model with D-galactose.Geldanamycin was isolated from the culture filtrates of a streptomyces and identified as the first known benzoquinoid ansamycin antibiotic, which has potent antitumor and antivirus activity. We studied the pharmacokinetics in Beagle dogs with solid phase extraction - HPLC method.
Keywords/Search Tags:cellular senescence, premature senescence, D-galactose, free radicals, cell cycle, geldanamyicn, pharmacokinetics
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