Metabolic profiling of chronic cadmium exposure in the rat

A confounding problem with studying the effects of environmental exposure t o contaminants in wild populations is that analytical techniques are invasi ve, particularly where the physiological effects of the toxin are assessed. In this study, a metabonomic approach to investigate the biochemical effec ts of chronic oral exposure to environmentally realistic doses of CdCl2 (lo w, 8 mg/kg; high, 40 mg/kg) is presented. H-1 NMR spectra of urine from exp osed animals were analyzed using pattern recognition methods to identify bi omarkers for a 94 day exposure period. Creatinuria and both increased excre tion 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 (M AS) H-1 NMR spectroscopy was used alongside conventional analytical techniq ues to investigate intact tissue directly. According to atomic absorption s ectroscopy, kidney tissue accumulated 26.8 +/- 2.5 mug of Cd2+/g dry wt (lo w) and 75.9 +/- 4.3 mug of Cd2+/g dry wt (high). Using high-resolution MAS H-1 NMR spectroscopy altered lipid content was detected in kidneys from ani mals exposed to Cd2+. However, unlike acute exposure, no testicular damage was evident. This systemic approach to metabolism demonstrated the differen t physiological effects of chronic subacute compared with an acute exposure to Cd2+.