Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy
ABSTRACT Heavy metals are known for their associated nephrotoxicity and nickel is no exception. An integrated metabonomic approach, based on high-resolution 1H NMR spectroscopy, was applied to determine the acute biochemical effects of NiCl2 on the renal tissues of rats. Kidney homogenates from rats treated with NiCl2 at two dose levels (4 and 20 mg kg−1 b.w., i.p.) and those from controls were analysed using 1H NMR spectroscopy and also assessed for antioxidant parameters at days 1, 3 and 5 post-dose. The major metabolite changes corresponding to nickel exposure were related to amino acids, osmolytes and energy metabolites. Differential responses were observed in 1H NMR spectra with exposure to low and high doses of NiCl2. For high doses, 1H NMR spectral analysis revealed alterations in renal tissues, along with damage to the cortical and papillary region and depletion of renal osmolytes such as betaine, trimethyl amine oxide, myo-inositol and taurine, which persisted until day 5 post-dose. The metabolite profile of 1H NMR spectra obtained from animals treated with lower dose of NiCl2 initially increased as an immediate stress response and then showed signs of recovery with the passage of time. NMR spectral analysis was well corroborated with histopathological and oxidative stress results. Nickel-induced oxidative stress was observed in both groups of animals with increased levels of antioxidant parameters at initial time points, but continued to increase in the high-dose group. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity. Copyright © 2011 John Wiley & Sons, Ltd.
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ABSTRACT: This article examines the actions of taurine on models of renal dysfunction, the potential mechanisms of taurine action and the possible clinical significance of these findings. Our laboratory has written previously on the role of taurine in renal function and we have focused upon the normal physiology of the kidney and on the mechanisms and regulation of the renal transport of taurine. This review is a distinct change of emphasis in that we describe a number of studies which have evaluated various aspects of renal dysfunction, including hypertension and proteinuria, specific glomerular and tubular disorders, acute and chronic renal conditions, urinary tract conditions including infection and nephrolithiasis, and diabetic nephropathy. The subject of chronic kidney disease and renal transplantation will also be examined relative to β amino acid. The studies evaluated will be mainly recent ones, recognizing that older reviews of the role of this taurine in the kidney are available.Amino Acids 05/2012; 46(1). DOI:10.1007/s00726-012-1314-y · 3.65 Impact Factor
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ABSTRACT: Mycophenolate mofetil (MMF) per se is not known to have negative effects on the kidney. MMF alone or in combination with sirolimus, can be the basis of calcineurin inhibitor (CNI)-free, kidney sparing drug protocols. However, long-term outcomes in patients on MMF/SRL seem to be inferior to those treated with regimens that include the CNI tacrolimus (TAC) due to an increased risk of allo-immune reactions. Interestingly, potential enhancement of the negative effects of SRL and TAC on the kidney by MMF has never been considered. It was our aim to study the effects of TAC, SRL and MMF alone and evaluate their interactions when combined on the rat kidney. For this purpose we used a comprehensive molecular marker approach including measurements of urinary 8-isoprostane concentrations (oxidative stress marker) and changes of urinary metabolite patterns ((1)H-NMR spectroscopy) and comparing these markers to renal function (glomerular filtration rate (GFR)) and morphologic alterations (histology). While MMF alone did not impact GFR, its interaction with SRL and TAC led to a significant decrease of rats' renal function. The decline went in parallel with a significant increase in urinary isoprostane concentrations and an enhancement of negative effects on urinary metabolite patterns. In broad summary, the present study showed that MMF may enhance the negative effects of TAC on kidney function and may even display nephrotoxic properties when combined with SRL.PLoS ONE 01/2014; 9(1):e86202. DOI:10.1371/journal.pone.0086202 · 3.53 Impact Factor