Tribendimidine (TBD) is a broad-spectrum
anthelmintic drug that is also significantly effective in treating
clonorchiasis. In this study, the altered metabolomes of Clonorchis sinensis (C. sinensis) in rats after TBD administration were quantified by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) to explore the possible active sites of TBD against
clonorchiasis through altered metabolites and metabolic pathway analysis, and the results are expected to provide a target for the future design of anti-Clonorchis sinensis drugs. The worm burden reduction rate and scanning electron microscopy demonstrated that
praziquantel (PZQ, positive control drug) and TBD had significant effects on C. sinensis in rats
after treatment at a single dose of 200 mg/kg for 24 h. For the MS-based metabolomic analysis, a total of 173 standard metabolites (126
amino acids, 10
phospholipids and 37
fatty acids) were utilized as a reference metabolite database for metabolome identification. In total, 32
amino acids, 71
phospholipids and 27
fatty acids were detected in the C. sinensis of each group. Among these metabolites, 10
amino acids were significantly decreased in both
drug-treated groups. Four lysophosphatidyl cholines (LPCs), six lysophosphatidyl
ethanolamines (LPEs) and one
phosphatidyl inositol (PI) were significantly increased
after treatment with TBD. There were no significant changes in
fatty acids among the control group and the two
drug-treated groups. The results indicated that TBD administration caused a decrease in
amino acids involved in the metabolic pathways of energy consumption and an increase in
lysophospholipids, which are the hydrolysis products of phospholipase2 (PLA2) in the
phospholipid metabolic pathways. The increased
lysophospholipid content can destroy the cell membrane, increase membrane permeability, and even cause exposure to internal
antigens that can be attacked by host
antibodies. Perhaps the destroyed membrane, the exposed internal
antigens and the consumed energy are the cause of the damage and death of C. sinensis after TBD administration. This is an interesting problem that can be examined in future research.