Characterization of urinary metabolites as biomarkers of colistin-induced nephrotoxicity in rats by a liquid chromatography/mass spectrometry-based metabolomics approach
| Autor: | Jae-Gook Shin, Dong-Hyun Kim, Eun Sook Jeong, Yong-Bum Kim, Jung-Hwa Oh, Kyoung-Sik Moon, Gabin Kim, Jayoung Jeong, Ho-Sook Kim |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Purine Male 030106 microbiology Pharmacology Toxicology Creatine Nephrotoxicity Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Tandem Mass Spectrometry medicine Animals Metabolomics Tissue Distribution Amino Acids Acetylcarnitine Chromatography High Pressure Liquid Polypeptide antibiotic Creatinine Kidney Colistin General Medicine Anti-Bacterial Agents 030104 developmental biology medicine.anatomical_structure chemistry Biochemistry Multivariate Analysis Kidney Diseases Biomarkers medicine.drug |
| Zdroj: | Toxicology letters. 248 |
| ISSN: | 1879-3169 |
| Popis: | Colistin is a polypeptide antibiotic that effectively treats infections caused by multidrug-resistant Gram-negative bacteria, but its clinical use is limited due to nephrotoxicity. The purpose of the present study was to identify biomarkers of colistin-induced nephrotoxicity and to further characterize the mechanisms underlying this process by analyzing urinary metabolites using untargeted metabolomic approach. Rats receiving intraperitoneal administration of colistin sodium methanesulfonate (CMS) (25 or 50mg/kg) exhibited histopathological changes in the kidney and increased blood urea nitrogen levels. Additionally, the levels of phenylalanine, tryptophan, and tyrosine in the urine of the CMS-treated group were significantly higher than those of the control group, suggesting that colistin caused proximal tubular damage. Urinary acetylcarnitine and butyrylcarnitine levels also increased after CMS treatment, but the levels of purine metabolites and metabolites related to the tricarboxylic acid cycle were reduced. The most significant increase in the CMS-treated groups was observed in creatine levels. CMS-induced selective nephrotoxicity may be attributed to relatively high tissue concentrations of colistin in the kidney. Taken together, our results indicate that high levels of colistin in the kidney caused perturbations in the tricarboxylic acid cycle, amino acid metabolism, creatine metabolism, and purine metabolism and ultimately led to kidney injury. |
| Databáze: | OpenAIRE |
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