Exploration of the direct metabolic effects of mercury II chloride on the kidney of Sprague-Dawley rats using high-resolution magic angle spinning 1H NMR spectroscopy of intact tissue and pattern recognition.
Mercury II chloride (HgCl2) toxicity was investigated in Sprague-Dawley rats using high-resolution magic angle spinning (HRMAS) 1H NMR spectroscopy in conjunction with principal component analysis (PCA). Intact renal cortex and papilla samples from Sprague-Dawley rats treated with HgCl2 at two dose levels (0.5 and 2 mg/kg) and from matched controls (n=5 per group) were assessed at 48 h p.d. HgCl2) caused depletion of renal osmolytes such as glycerophosphocholine (GPC), betaine, trimethylamine N-oxide (TMAO), myo-inositol and taurine in both the renal cortex and the papilla. In addition, relatively higher concentrations of valine, isobutyrate, threonine and glutamate were observed in HgCl2-treated rats, particularly in the renal cortex, which may reflect a counterbalance response to the observed loss of other classes of renal osmolytes. Increased levels of glutamate were present in the cortex of treated rats, which may be associated with HgCl2-induced renal acidosis and disruption of the tricarboxylic acid cycle. A dose response was observed in both cortical and papillary tissue with increasing severity of metabolic disruption in the high dose group. 1H HRMAS NMR profiles of individual animals correlated well with conventional clinical chemistry and histology confirming the reproducibility of the technology and generating complementary molecular pathway information.
Wang
Yulan
Y
Biological Chemistry, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK.
Bollard
Mary E
ME
Nicholson
Jeremy K
JK
Holmes
Elaine
E
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008744:Methylamines / Q000378:metabolism; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013654:Taurine / Q000378:metabolism
D000596:Amino Acids; D008744:Methylamines; D013654:Taurine; D008627:Mercuric Chloride; C005855:trimethyloxamine