Metabonomics study of liver and kidney subacute toxicity induced by garidi-5 in rats

Objective:Metabonomics was used to analyze and explore the biomarkers and possible mechanisms of liver and kidney subacute toxicity induced by garidi-5 in rats.Methods:Taking garidi-5 as the target drug and SD rats as the research objects,each administration group except the normal group was intragastric administration of the corresponding drug solution for28 d.The serum,liver and kidney samples of rats were detected by metabolomics and characterized by principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)to identify the sensitive markers and metabolic pathways of liver and kidney subacute toxicity.Results:Metabolomics analysis showed that compared with the normal group(Z),the 52,64 and 54 different metabolites were identified in the serum,liver and kidney samples of garidi-5 high dose group(GG),which were mainly enriched in ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism,central carbon metabolism in cancer pathways.Conclusion:The preliminarily suggested that garidi-5 can damage the liver and kidney by affecting the ABC transporters,arginine and proline metabolism,nicotinate and nicotinamide metabolism pathways,etc.Trimethylamine N-oxide,L-pyroglutamic acid,glycine-betaine,xanthine,glutathione,L-leucine,cytidine,L-arginine,spermidine,urea,5-aminovaleric acid,creatine,L-glutamic acid,1-methylnicotinamide and S-adenosyl-L-methionine can be used as potential biomarkers of liver and kidney toxicity sensitivity.