A method and clearance pattern for in vitro metabolism of chlorinated paraffin in chicken liver microsomes based on serum promotion
It is an important basis for exploring their bioaccumulation mechanisms to study the metabolic clearance patterns of chlorinated paraffins(CPs)in animals.In vitro metabolism of target compounds by liver microsomes is an important means to simulate its metabolism in animals.By optimizing the method of CPs metabolism by chicken liver microsome in vitro,using serum as an additive agent,a high efficient method of CPs metabolism by chicken liver microsome in vitro was established.In this method,the volume of organic solvent dissolving the substrate could be as high as 3％of the total reaction volume,and the amount of serum added was one to ten times of the volume of substrate solution.After the termination of the reaction,there was no need to extract steps,and the method was simple,so that the rapid processing of samples was realized.The method was successfully applied to the study of CPs clearance by chicken liver microsomes in vitro.The results showed that under serum-free conditions,the metabolic clearance rates of all short chain chlorinated paraffins(SCCPs)with molecular formula homologues were lower than 20％when chicken liver microsomes were incubated with substrates for 90 min.However,after adding a small amount of serum as the carrier of substrate,the metabolic clearance ratio of SCCPs molecular formula homologues was significantly improved within the same incubation time,and the metabolic clearance ratio of C11Cl6-8 was even more than 80％.This is the first time to reveal the metabolic clearance of CPs by liver microsomes in vitro:The metabolic clearance of CPs by chicken liver microsomes decreased with the increase of substrate concentration,CPs carbon chain length and their number of chlorine atoms.This study will provide an efficient method for the study of CPs metabolism by animal liver microsomes in vitro.Meanwhile,it will also provides a new method reference for the study of liver microsome metabolism of other hydrophobic compounds in vitro.
serumchlorinated paraffinsliver microsomesmetabolic clearance ratio
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