The mechanism of galactosamine toxicity revisited; a metabonomic study.

1H NMR spectroscopy was used to investigate the metabolic effects of the hepatotoxin galactosamine (galN) and the mechanism by which glycine protects against such toxicity. Rats were acclimatized to a 0 or 5% glycine diet for 6 days and subsequently administered vehicle, galN (500 mg/kg), glycine (5% via the diet), or both galN and glycine. Urine was collected over 12 days prior to administration of galN and for 24 hours thereafter. Serum and liver tissue were sampled on termination, 24 hours post-dosing. The metabolic profiles of biofluids and tissues were determined using high-field 1H NMR spectroscopy. Orthogonal-projection to latent structures discriminant analysis (O-PLS-DA) was applied to model the spectral data and enabled the hepatic, urinary, and serum metabolites that discriminated between control and treated animals to be determined. Histopathological data and clinical chemistry measurements confirmed the protective effect of glycine. The level of N-acetylglucosamine (glcNAc) in the post-dose urine was found to correlate strongly with the degree of galN-induced liver damage, and the urinary level of glcNAc was not significantly elevated in rats treated with both galN and glycine. Treatment with glycine alone was found to significantly increase hepatic levels of uridine, UDP-glucose, and UDP-galactose, and in view of the known effects of galactosamine, this suggests that the protective role of glycine against galN toxicity might be mediated by changes in the uridine nucleotide pool rather than by preventing Kupffer cell activation. Thus, we present a novel hypothesis: that administration of glycine increases the hepatic uridine nucleotide pool which counteracts the galN-induced depletion of these pools and facilitates complete metabolism of galN. These novel data highlight the applicability of NMR-based metabonomics in elucidating multicompartmental metabolic consequences of toxicity and toxic salvage.

Cropping systems for phytoremediation of phosphorus-enriched soils.

Eutrophication of freshwater bodies is frequently attributed to elevated phosphorus (P) concentrations in surface runoff from P-enriched agricultural soils. Forage and grain-cropping systems were compared for their effectiveness at remediating P-enriched soils. At each of four locations, one of three forage systems (Forage I = cereal rye silage and corn silage annually; Forage II = alfalfa; Forage III = annual ryegrass and corn silage annually) and the grain system (corn, small grain, and soybean rotation) were maintained for 3 yr on soils with five distinct initial soil P concentrations that were established by using four annual applications (1994-1997) of five different rates (0, 100, 200, 300, and 400 kg total P ha(-1) y(-1)) of poultry manure, dairy manure, or commercial fertilizer. Across all manure P treatments at all locations, the forage systems had greater removal of P than the grain system. Soil P concentration changes (2001-2004) did not reflect differences in crop P removal. Few significant reductions in soil P concentration were observed for either crop system. When reductions did occur, they were for the more highly enriched soil P treatments. No significant reductions in soil P concentration have occurred for the lowest manure P treatments. Considerable variability in crop P concentrations was observed among species at locations and among years produced. However, crop P concentrations did increase uniformly as soil P concentration increased, indicating that luxury consumption of P does occur in agronomic species produced on P-enriched soils.