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
S. Garrod et al., 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, MAGN RES M, 45(5), 2001, pp. 781-790
Citations number
41
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Medical Research Diagnosis & Treatment
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.