Preclinical Long-term Magnetic Resonance Imaging Study of Silymarin Liver-protective Effects

Yeon Ji Chae; Hwon Heo; Chul-Woong Woo; Sang-Tae Kim; Jae-Im Kwon; Monica Young Choi; Yu Sub Sung; Kyung Won Kim; Jeong Kon Kim; Yoonseok Choi; Dong-Cheol Woo

doi:10.14218/JCTH.2021.00499

Preclinical Long-term Magnetic Resonance Imaging Study of Silymarin Liver-protective Effects

J Clin Transl Hepatol. 2022 Dec 28;10(6):1167-1175. doi: 10.14218/JCTH.2021.00499. Epub 2022 Apr 13.

Authors

Yeon Ji Chae¹, Hwon Heo¹, Chul-Woong Woo², Sang-Tae Kim², Jae-Im Kwon², Monica Young Choi¹, Yu Sub Sung³, Kyung Won Kim⁴, Jeong Kon Kim⁴, Yoonseok Choi⁵, Dong-Cheol Woo^{1

2}

Affiliations

¹ Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
³ Clinical Research Center, Asan Medical Center, Seoul, Republic of Korea.
⁴ Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁵ Medical Research Institute, Gangneung Asan Hospital, Gangneung-si, Gangwon-do, Republic of Korea.

Abstract

Background and aims: Efficacy evaluations with preclinical 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.

Methods: TAA was injected three times a week for 8 weeks to generate a disease model (TAA group). In the TAA and silymarin-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 (AUC_tmax) and T₂* 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 silymarin treatment. Negative correlations between either AUC_tmax or T₂* 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.

Keywords: Liver fibrosis; Magnetic resonance imaging; Silymarin; T1-weighted dynamic contrast-enhanced; T2*.