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A metabonomic study on the biochemical effects of doxorubicin in rats using (1)H-NMR spectroscopy.
- Source :
-
Journal of toxicology and environmental health. Part A [J Toxicol Environ Health A] 2009; Vol. 72 (6), pp. 374-84. - Publication Year :
- 2009
-
Abstract
- Metabonomic investigation of doxorubicin (adriamycin) was carried out in male Sprague-Dawley rats using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistics. Urine samples (d -1 to 7) from rats treated with doxorubicin at two dose levels (5 or 15 mg/kg body weight) were collected at each time point and doxorubicin-induced biomarkers were examined. Of metabolites, early elevated biochemical changes were observed in trimethylamine N-oxide (TMAO) levels suggesting renal dysfunction. Perturbation in TMAO was maximal in the low-dose group at 48 h post dose (p.d.) and returned to control at 168 h p.d., indicating recovery from renal toxicity induced by doxorubicin. After doxorubicin administration, the high-dose group was divided into low and high responders at 48 h and further divided into high, moderate, and no recovery animals at 96 h, indicating individual susceptible response to drug-induced toxicity. Urinary increases in glucose, lactate, alanine, and valine suggested progression of renal damage resulting in glycosuria, lactic aciduria, and aminoaciduria up to 168 h in the high-dose group. Urinary elevation of creatine and phenylacetylglycine (PAG) together with reduction of N-methylnicotinic acid (NMNA) and hippurate levels was suggestive of liver injury in the high-dose group. Impairment of energy metabolism was also indicated by decreased levels of tricarboxylic acid cycle intermediates in urine of rats treated with high-dose doxorubicin. This study highlights the applicability of NMR-based metabonomics with multivariate statistics for monitoring biomarkers produced by doxorubicin treatments.
- Subjects :
- Animals
Biomarkers
Doxorubicin metabolism
Doxorubicin urine
Kidney metabolism
Kidney Diseases metabolism
Least-Squares Analysis
Magnetic Resonance Spectroscopy
Male
Methylamines metabolism
Methylamines urine
Multivariate Analysis
Principal Component Analysis
Rats
Rats, Sprague-Dawley
Doxorubicin toxicity
Kidney drug effects
Kidney Diseases chemically induced
Metabolomics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-7394
- Volume :
- 72
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of toxicology and environmental health. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 19199144
- Full Text :
- https://doi.org/10.1080/15287390802647195