Case Study And Mechanism Investigation On Drug-Induced Liver Injury Based On Drug-Drug Interaction

AIMS Based on drug-drug interaction to analysis and investigate drug-induced liver injury (DILI) and the underlying mechanism; and further investigate the mechanism of Yuanhua (Flos Genkwa, FG) and Gancao (Radix et Rhizoma Glycyrrhizae, RRG) induced liver injury in mice.METHODS In case study, clinical pharmacists carried out a series of clinical pharmacy work, and the relationship of drug-drug interaction and DILI was analyzed by collecting data of clinical examination, laboratory examination, drug usage, drugs interactions, and disease prognosis. With the support of literature, the possible mechanism of DILI was further evaluated based on drug-drug interaction. In mechanism study, FG and RRG were given to mice to investigate the mechanism of DILI. A total of35female KunMing mice were divided into5groups with7in each; mice in control group were orally given saline, mice in FG and RRG group were administered FG (15g·kg-1·d-1) and RRG (15g·kg-1·d-1); while mice in FG and RRG mixture group (ratio1:1or1:3) were treated with FG (7.5g·kg-1·d-1)+RRG (7.5g·kg-1·d-1) or FG (3.75g·kg-1·d-1)+RRG (11.25g·kg-1·d-1), respectively. Drugs were orally administered for7days. After the final drugs administration, total bile acid (TBA) content in liver was determined by enzymatic cycling, the liver was removed for pathological evaluation, and protein expression of sodium taurocholate cotransporting plypeptide (Ntcp) was also analyzed by Western blot. Data were obtained and analyzed using statistical software to evaluate the correlation.RESULTS When drugs were co-administered inappropriately, drugs interaction may alter the expression and/or function of drug metabolic enzyme and transporters, which may further induce DILI. DILI was commonly induced by anti-tuberculosis drugs, traditional Chinese medicine, and antibacterial agents. Among them, research about DILI induced by traditional Chinese medicine was relatively lagging. The experimental results showed that FG and RRG co-administration can induce liver injury with the significant increase of Ntcp expression and TBA content, Ntcp alteration was correlated with TBA (r=0.963), and the alteration of Ntcp and TBA was significantly correlated with the degree of liver injury (r=0.947)CONCLUSION Drugs co-administration and drugs interaction may increase the risk of DILI; FG and RRG co-administration significantly increased the Ntcp expression in liver, and thus lead to the liver accumulation of TBA, which may be one of the mechanism of FG and RRG induced liver injury.