Metabonomic study of genkwa flos-induced hepatotoxicity and effect of herb-processing procedure on toxicity.
A urinary metabonomic approach based on ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic disturbances caused by the administration of Genkwa Flos (GF) to rats. Potential biomarkers of GF-induced toxic effects were screened out and identified, and the underlying toxicological mechanism as well as the detoxification of vinegar-processing procedure on this herb was discussed. Urine samples were analyzed by the established UPLC-MS method. With the help of serum biochemistry and histopathology results, metabolic disturbances induced by the exposure to GF and the detoxification of processing procedure were confirmed. The differences in the metabolic profiles of healthy and treated rats were clearly discriminated with the principal component analysis of the chromatographic data. Eight significantly changed metabolites were identified and interpreted as biomarkers for the hepatotoxicity and detoxification of processing procedure. This study indicated that a UPLC-MS-based metabonomic analysis of urine samples could be considered as a promising tool to predict the hepatotoxicity induced by the GF and the detoxification of traditional vinegar-processing procedure on this herb.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Lulu
L
Geng
Chao
C
Ma
Li
L
Zhang
Guoguang
G
Yang
Yan
Y
Cui
Dan
D
Su
Xu
X
Zhao
Zhenzhen
Z
Liu
Kaishun
K
Bi
Xiaohui
X
Chen
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000652:urine; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D032364:Daphne / Q000633:toxicity*; D035264:Flowers / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D016482:Urinalysis
D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase