title: Metabolic profiling of chronic cadmium exposure in the rat.
abstract: A confounding problem with studying the effects of environmental exposure to contaminants in wild populations is that analytical techniques are invasive, particularly where the physiological effects of the toxin are assessed. In this study, a metabonomic approach to investigate the biochemical effects of chronic oral exposure to environmentally realistic doses of CdCl2 (low, 8 mg/kg; high, 40 mg/kg) is presented. 1H NMR spectra of urine from exposed animals were analyzed using pattern recognition methods to identify biomarkers for a 94 day exposure period. Creatinuria and both increased excretion and complexation of citrate was detected after 19 days of exposure in both exposure groups. This was accompanied by a decrease in plasma Ca2+/Mg2+ ratio in blood plasma after 94 days. Post mortem, magic angle spinning (MAS) 1H NMR spectroscopy was used alongside conventional analytical techniques to investigate intact tissue directly. According to atomic absorption spectroscopy, kidney tissue accumulated 26.8 +/- 2.5 microg of Cd2+/g dry wt (low) and 75.9 +/- 4.3 microg of Cd2+/g dry wt (high). Using high-resolution MAS 1H NMR spectroscopy altered lipid content was detected in kidneys from animals exposed to Cd2+. However, unlike acute exposure, no testicular damage was evident. This systemic approach to metabolism demonstrated the different physiological effects of chronic subacute compared with an acute exposure to Cd2+.
authors.affiliation: Biological Chemistry, Biomedical Sciences Division, The Sir Alexander Fleming Building, Exhibition Road, Imperial College of Science, Medicine and Technology, London, SW7 2AZ, UK. j.griffin@ic.ac.uk
authors.forename: J L
authors.initials: JL
authors.lastname: Griffin
authors.forename: L A
authors.initials: LA
authors.lastname: Walker
authors.forename: R F
authors.initials: RF
authors.lastname: Shore
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D019256:Cadmium Chloride / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D013737:Testis / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D019256:Cadmium Chloride