Font Size: a A A

Metabonomics For The Profiling Of Hepatic Injury Biomarkers Based On Mass Spectrometry

Posted on:2010-12-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y P LinFull Text:PDF
GTID:1114360302495183Subject:Pharmaceutical Engineering
Abstract/Summary:PDF Full Text Request
Liver is the key organ for metabolism, because it is responsible for most of the anabolism, catabolism and transforlation in vivo. Some metabolic enzymes are only found in liver, so it's essential to investigate metabolic mechanisms of liver for the better perspective of hepatic diseases. Metabonomics broadly aims to measure the global, dynamic metabolic response of living systems to biological stimuli or genetic manipulation. It focuses on tracing systemic changes according to time in complex multicellular systems. In this dissertation, there is an integrated metabonomic platform established basing on liquid chromatography-mass spectrometry technique and chemometric methods for the profiling of hepatic injury biomarkers.Urine and bile pre- and post dose are collected for seven-day long from a hepatotoxic model of Wistar rat induced by a single oral dosage of carbon tetrachloride (CCl4). The fluctuations of these urinary components characterize the disfunction of Kerbs Circle as well as an energy decline, proving an acute hepatotoxicity and nephrotoxicity right after the oral exposure of CCl4. Meanwhile, the excretion of bile is slowed down and the concentrations of phosphatidylcholine in bile are elevated.Serums of hepatitis B virus infected people and healthy people are compared through the metabonomic platform. Some components in serum including creatinine, L-Threonine, L-Tyrosine and glycohenodeoxycholic acid or its isomer glycodeoxycholic acid are upregulated after hepatitis B infection. The results also reveal individual variations of clinical samples, which increase challenges of metabonomic investigation.After comparing the hepatic injury biomarkers of hepatotoxic animal model and hepatitis B infected human, we find out that the energy circle is slowed down and biosythesis of bile acid is badly affected if the hepatic cell is injured. The current study is another approach of metabonomics applied in toxicology and clinical diagnosis.
Keywords/Search Tags:metabonomics, mass spectrometry, hepatic injury biomarkers, carbon tetrachloride, hepatotoxic animal model, hepatitis B virus infection
PDF Full Text Request
Related items