Background and Aims:Efficacy evaluations with preclini-cal magnetic resonance imaging(MRI)are uncommon,but MRI in the preclinical phase of drug development provides information that is useful for longitudinal monitori...Background and Aims:Efficacy evaluations with preclini-cal magnetic resonance imaging(MRI)are uncommon,but MRI in the preclinical phase of drug development provides information that is useful for longitudinal monitoring.The study aim was to monitor the protective effectiveness of silymarin with multiparameter MRI and biomarkers in a thioacetamide(TAA)-induced model of liver injury in rats.Correlation analysis was conducted to assess compare the monitoring of liver function by MRI and biomarkers.Meth-ods:TAA was injected three times a week for 8 weeks to generate a disease model(TAA group).In the TAA and sily-marin-treated(TAA-SY)groups,silymarin was administered three times weekly from week 4.MR images were acquired at 0,2,4,6,and 8 weeks in the control,TAA,and TAA-SY groups.Results:The area under the curve to maximum time(AUCtmax)and T_(2)*values of the TAA group decreased over the study period,but the serological markers of liver abnormality increased significantly more than those in the control group.In the TAA-SY group,MRI and serological biomarkers indicated attenuation of liver function as in the TAA group.However,pattern changes were observed from week 6 to comparable levels in the control group with si-lymarin treatment.Negative correlations between either AUCtmax or T_(2)*values and the serological biomarkers were observed.Conclusions:Silymarin had hepatoprotective effects on TAA-induced liver injury and demonstrated the usefulness of multiparametric MRI to evaluate efficacy in preclinical studies of liver drug development.展开更多
基金the Asan Institute of Life Sciences,Asan Medical Center,Republic of Korea(2020IL0026-1)the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(2018R1A2B2007694)and the Ministry of Education(2020R1I1A1A01058302).
文摘Background and Aims:Efficacy evaluations with preclini-cal magnetic resonance imaging(MRI)are uncommon,but MRI in the preclinical phase of drug development provides information that is useful for longitudinal monitoring.The study aim was to monitor the protective effectiveness of silymarin with multiparameter MRI and biomarkers in a thioacetamide(TAA)-induced model of liver injury in rats.Correlation analysis was conducted to assess compare the monitoring of liver function by MRI and biomarkers.Meth-ods:TAA was injected three times a week for 8 weeks to generate a disease model(TAA group).In the TAA and sily-marin-treated(TAA-SY)groups,silymarin was administered three times weekly from week 4.MR images were acquired at 0,2,4,6,and 8 weeks in the control,TAA,and TAA-SY groups.Results:The area under the curve to maximum time(AUCtmax)and T_(2)*values of the TAA group decreased over the study period,but the serological markers of liver abnormality increased significantly more than those in the control group.In the TAA-SY group,MRI and serological biomarkers indicated attenuation of liver function as in the TAA group.However,pattern changes were observed from week 6 to comparable levels in the control group with si-lymarin treatment.Negative correlations between either AUCtmax or T_(2)*values and the serological biomarkers were observed.Conclusions:Silymarin had hepatoprotective effects on TAA-induced liver injury and demonstrated the usefulness of multiparametric MRI to evaluate efficacy in preclinical studies of liver drug development.
