ABSTRACT
OBJECTIVE Dynamics of serum and urine metabolites in hepatic injury rats induced by ethanolic extract from Rhizoma Dioscoreae Bulbiferae(RDB)was investigated by 1H-NMR-based metabo?nomic methods in order to discover early biomarkers of liver toxicity induced by RDB. METHODS Rats were ig adminisetred with RDB at a dose of 5 g·kg-1 for 28 d. Rats were sacrificed 3,7,14 and 28 d af?ter RDB administration,as well as after a recovery period,respectively. Blood was taken for routine bio?chemical analysis by an automatic biochemical analyzer. Liver/body mass indexes were calculated ,and liver pathological changes were observed with hematoxylin-eosin staining. Urine samples were collected before and 3,7,14 and 28 d after RDB administration,respectively,as well as after withdrawal. Metabo?nomic analysis was carried out for serum and urine samples. Principal component analysis and orthogonal partial least squares-discriminant analysis were used for screening and identifiying early biomarkers. RESULTS Compared with the control group,total bilirubin (TB) and total cholesterol (TC) values were increased in 3-28 d in RDB group(P<0.05,P<0.01). Total bile acid(TBA)was elevated in 7-28 d (P<0.05,P<0.01). TB,TC and TBA became normal after discontinuation with RDB. There was no significant difference between RBD-treated group and control group in the activity of glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase,and the content of glucose also was not different between the two groups. The ratio of liver/body mass was elevated at 3-28 d(P<0.01)but returned to normal after withdraval of RDB. The enlargement and necrosis of hepatocytes were observed 7 d after RDB administration,and lesion degree was aggravated with the extension of RDB delivery time. Meta?bonomic analysis showed that the serum lipids (low density lipoprotein/very low density lipoprotein (LDL/VLDL),glutamic acid,choline phosphate and glycerolphosphatecholine were increased in the early stage. Pyruvate and N-acetylglutamate were decreased in urine. These metabolites became normal 7 d after discontinuation with RDB. CONCLUSION The serum lipids (LDL/VLDL),glutamic acid,glycerol phosphate choline,as well as urine pyruvic acid salt and N-acetyl glutamate may be used as the early biomarkers for liver toxicity induced by RDB.
ABSTRACT
MicroRNAs (miRNAs) are a new class of endogenous, single-strand, noncoding small RNAs. MiRNAs play an important regulatory role in a variety of pathological and physiological process, such as cell proliferation and apoptosis, organ development and differentiation and tumorigenesis and so on. It has been found that circulating miRNAs are also stably and specially expressed in serum or plasma and other body fluids. Circulating miRNAs could be taken as noninvasive and new biomarkers for evaluating the drug-induced target organ injury, which may play a vital role in monitoring the drug toxicity at the early stage.