Effects of feeding and body weight loss on the 1H-NMR-based urine metabolic profiles of male Wistar Han Rats: Implications for biomarker discovery

For almost two decades, 1H-NMR spectroscopy has been used as an ‘open’ system to study the temporal changes in the biochemical composition of biofluids, including urine, in response to adverse toxic events. Many of these in vivo studies have reported changes in individual metabolites and patterns of metabolites that correlated with toxicological changes. However, many of the proposed novel biomarkers are common to a number of different types of toxicity. These may therefore reflect non-specific effects of toxicity, such as weight loss, rather than a specific pathology. A study was carried out to investigate the non-specific effects on urinary metabolite profiles by administering four hepatotoxic compounds, as a single dose, to rats at two dose levels: hydrazine hydrate (0.06 or 0.08 g kg−1), 1,2-dimethylhydrazine (0.1 or 0.3 g kg−1), α-napthylisothiocyanate (0.1 or 0.15 g kg−1) and carbon tetrachloride (1.58 or 3.16 g kg−1). The study included weight-matched control animals along with those that were dose...