High-resolution H-1 NMR and magic angle spinning NMR spectroscopic investigation of the biochemical effects of 2-bromoethanamine in intact renal and hepatic tissue

The metabolic consequences of xenobiotic-induced toxicity were investigated using high-resolution magic angle spinning (MAS) NMR spectroscopy of intac t tissue. Renal papillary necrosis (RPN) was induced in Sprague-Dawley rats (n = 12) via a single i,p, dose of 250 mg/kg 2-bromoethanamine (BEA) hydro bromide. At 2, 4, 6, and 24 h after treatment with BEA, three animals were killed and tissue samples were obtained from liver, renal cortex, and renal medulla, Tissue samples were also removed at 2 and 24 h from matched contr ols (n = 6), H-1 MAS NMR spectroscopic techniques were used to analyze samp les of intact tissue (similar to 10 mg). Decreased levels of nonperturbing renal osmolytes (glycerophosphocholine, betaine, and myoinositol) were obse rved in the renal papilla of BEA-treated animals at 6 and 24 h postdose (p. d.), concomitant with a relative increase in the tissue concentration of cr eatine, Increased levels of glutaric acid were found in all tissues studied in BEA-treated animals at 4 and 6 h p.d., indicating the inhibition of mit ochondrial fatty acyl CoA dehydrogenases and mitochondrial dysfunction, Inc reased levels of trimethylamine-N-oxide occurred in the renal cortex at 6 h p.d, Changes in the metabolite profile of liver included an increase in th e relative concentrations of triglycerides, lysine, and leucine, The novel application of H-1 MAS NMR to the biochemical analysis of intact tissues fo llowing a toxic insult highlights the potential of this technique as a toxi cological probe in providing a direct link between urinary biomarkers of to xicity and histopathological evaluation of toxicological lesions. (C) 2001 Wiley-Liss, Inc.