AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic microsomes.METHODS Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF an...AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic microsomes.METHODS Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF and PB and the non-induced microsome asthe control.The enzymatic kinetic parameters ofpropranolol enantiomers were calculated byregression analysis of Lineweaver-Burk plots.Propranolol concentrations were assayed byHPLC.RESULTS A RP-HPLC method was developed todetermine propranolol concentration in rathepatic microsomes.The linearity equations forR（+）-propranolol and S（-）-propranolol wereA=705.7C+311.2C（R = 0.9987）and A= 697.2C+311.4C（R = 0.9970）respectively.Recoveriesof each enantiomer were 98.9%,99.5%,101.0%at 60 μmol/L,120 μmol/L,240 μmol/Lrespectively.At the concentration level of120 μmol/L,propranolol enantiomers weremetabolized at different rates in differentmicrosomes.The concentration ratio R（+）/S（-）of control and PB induced microsomesincreased with time,whereas that of microsomeinduced by BNF decreased.The assayed enzymeparameters were:1.Km.Control group:R（+）30+<sub>8</sub>,S（-）18+<sub>5</sub>;BNFgroup:R（+）34+3,S（-）39±7;PB group:R（+）38±17,S（-）36±10.2.Vmax.Control group:R（+）1.5+0.2,S（-）2.9±0.3;BNF group:R（+）3.8±0.3,S（-）3.3±0.5;PB group:R（+）0.07±0.03,S（-）1.94±0.07.3.Clint.Control group:R（+）60±3,S（-）170±30;BNF group:R（+）111.0±1,S（-）84± 5;PBgroup:R（+）2.0±2,S（-）56.0±1.Theenzyme.parameters compared with unpaired ttests showed that no stereoselectivity wasobserved in enzymatic affinity of threemicrosomes to enantiomers and their catalyticabilities were quite different and hadstereoselectivities.Compared with the control,microsome induced by BNF enhanced enzymeactivity to propranolol R（+）-enantiomer,andmicrosome induced by PB showed less enzymeactivity to propranolol S（-）-enantiomer whichremains the same stereoselectivities as that ofthe control.CONCLUSION Enzyme activity centers of themicrosome were changed in composition andregioselectivity after the induction of BNF andPB,and the stereoselectivities of propranololcytochrome P450 metabolism in rat hepaticmicrosomes were likely due to thestereoselectivities of the catalyzing function inenzyme.CYP1A subfamily induced by BNFexhibited pronounced contribution to propranololmetabolism with stereoselectivity to R（+）-enantiomer.CYP2B subfamily induced by PBexhibited moderate contribution to propranololmetabolism,but still had the stereoselectivity ofS（-）-enantiomer.展开更多
The use of waste crumb rubber powder as a modifier for modified asphalt can recycle waste rubber to ease pressure on the environment and improve the performance of asphalt. Diffusion of components of asphalt into wast...The use of waste crumb rubber powder as a modifier for modified asphalt can recycle waste rubber to ease pressure on the environment and improve the performance of asphalt. Diffusion of components of asphalt into waste rubber is of vital importance to improve the performance of rubber modified asphalt,while the related researches are scarce. Diffusion of components of asphalt into waste rubber at different temperatures has been investigated in this work. Rectangle rubber was immersed in asphalt at certain temperature for a period of time. And the mass increment of rubber was measured to determine the diffusion rate of components of asphalt into rubber. The experimental results indicated that the diffusion rate of components of asphalt into waste rubber increases along the temperature,but the diffusion rate of components of fractions oil which is distillated from catalytic cracking slurry is much higher than that of components of asphalt. Compared with asphalt,fractions oil enjoys lower viscosity and better permeability with higher content of saturates and aromatics. All the characteristics are contributed to the efficient diffusion of components of fractions into waste rubber.展开更多
基金the National Natural Science Foundation of China,No.39370805.
文摘AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic microsomes.METHODS Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF and PB and the non-induced microsome asthe control.The enzymatic kinetic parameters ofpropranolol enantiomers were calculated byregression analysis of Lineweaver-Burk plots.Propranolol concentrations were assayed byHPLC.RESULTS A RP-HPLC method was developed todetermine propranolol concentration in rathepatic microsomes.The linearity equations forR（+）-propranolol and S（-）-propranolol wereA=705.7C+311.2C（R = 0.9987）and A= 697.2C+311.4C（R = 0.9970）respectively.Recoveriesof each enantiomer were 98.9%,99.5%,101.0%at 60 μmol/L,120 μmol/L,240 μmol/Lrespectively.At the concentration level of120 μmol/L,propranolol enantiomers weremetabolized at different rates in differentmicrosomes.The concentration ratio R（+）/S（-）of control and PB induced microsomesincreased with time,whereas that of microsomeinduced by BNF decreased.The assayed enzymeparameters were:1.Km.Control group:R（+）30+<sub>8</sub>,S（-）18+<sub>5</sub>;BNFgroup:R（+）34+3,S（-）39±7;PB group:R（+）38±17,S（-）36±10.2.Vmax.Control group:R（+）1.5+0.2,S（-）2.9±0.3;BNF group:R（+）3.8±0.3,S（-）3.3±0.5;PB group:R（+）0.07±0.03,S（-）1.94±0.07.3.Clint.Control group:R（+）60±3,S（-）170±30;BNF group:R（+）111.0±1,S（-）84± 5;PBgroup:R（+）2.0±2,S（-）56.0±1.Theenzyme.parameters compared with unpaired ttests showed that no stereoselectivity wasobserved in enzymatic affinity of threemicrosomes to enantiomers and their catalyticabilities were quite different and hadstereoselectivities.Compared with the control,microsome induced by BNF enhanced enzymeactivity to propranolol R（+）-enantiomer,andmicrosome induced by PB showed less enzymeactivity to propranolol S（-）-enantiomer whichremains the same stereoselectivities as that ofthe control.CONCLUSION Enzyme activity centers of themicrosome were changed in composition andregioselectivity after the induction of BNF andPB,and the stereoselectivities of propranololcytochrome P450 metabolism in rat hepaticmicrosomes were likely due to thestereoselectivities of the catalyzing function inenzyme.CYP1A subfamily induced by BNFexhibited pronounced contribution to propranololmetabolism with stereoselectivity to R（+）-enantiomer.CYP2B subfamily induced by PBexhibited moderate contribution to propranololmetabolism,but still had the stereoselectivity ofS（-）-enantiomer.
基金supported by State Key Laboratory of Heavy Oil Processing,China University of Petroleum
文摘The use of waste crumb rubber powder as a modifier for modified asphalt can recycle waste rubber to ease pressure on the environment and improve the performance of asphalt. Diffusion of components of asphalt into waste rubber is of vital importance to improve the performance of rubber modified asphalt,while the related researches are scarce. Diffusion of components of asphalt into waste rubber at different temperatures has been investigated in this work. Rectangle rubber was immersed in asphalt at certain temperature for a period of time. And the mass increment of rubber was measured to determine the diffusion rate of components of asphalt into rubber. The experimental results indicated that the diffusion rate of components of asphalt into waste rubber increases along the temperature,but the diffusion rate of components of fractions oil which is distillated from catalytic cracking slurry is much higher than that of components of asphalt. Compared with asphalt,fractions oil enjoys lower viscosity and better permeability with higher content of saturates and aromatics. All the characteristics are contributed to the efficient diffusion of components of fractions into waste rubber.
