The initial pathogenesis of cadmium induced renal toxicity

Abstract

The novel application of magic angle spinning 1 H NMR spectroscopy, coupled with pattern recognition techniques, has identified biochemical changes in lipid and glutamate metabolism that precede classical nephrotoxicity. These changes occurred in the bank vole (Clethrionomys glareolus) after chronic dosing, at a low level of exposure and at a renal Cd 2+ concentration (8.4 W Wg/g dry wt) that was nearly two orders of magnitude below the WHO critical organ concentration (200 W Wg/g wet wt). These early stage effects of Cd 2+ on the biochemistry of renal tissue may reflect adaptation mechanisms to the toxic insult or the preliminary stages of the toxicological cascade. ß

Ecological metabolomics: overview of current developments and future challenges

“…These studies have allowed the identification of some metabolites (acetilspermidine, glucose, histidine, l-methylhistidine, mannose) that can be used as biomarkers for Cu, Cd and Zn pollution in various animal species (Bundy et al 2004(Bundy et al , 2008Taylor et al 2009;Guo et al 2009). In rats, in addition to the changes in amino acid and sugar contents, a further abnormal metabolome composition has been observed as a result of Cd and Cu intake (Jones et al 2007;Lei et al 2008), and changes in lipid metabolism under high levels of As have also been observed (Griffin et al 2000). A tendency to increase the production of AMP, ADP and N-a-methylhistidine, and to generate an imbalance in metabolites related to energetics by reducing ATP levels has been reported in Lumbricus rubellus (Bundy et al , 2008.…”

“…Thus, if the aims are also to determine possible novel structures, the use of 1 HNMR is advisable. A set of recent partial ecometabolomic studies of polar metabolites has also permitted the identification of the metabolites and metabolic pathways affected by certain trace element polluting plants (Bailey et al 2003;Roessner et al 2006;Sarry et al 2006;Le Lay et al 2006;Sun et al 2008) and animals (Gibbs et al 1997;Griffin et al 2001Griffin et al , 2000Bundy et al 2007Bundy et al , 2004Jones et al 2008b;Taylor et al 2009;Guo et al 2009) (Table 2). These studies have allowed the identification of some metabolites (acetilspermidine, glucose, histidine, l-methylhistidine, mannose) that can be used as biomarkers for Cu, Cd and Zn pollution in various animal species (Bundy et al 2004(Bundy et al , 2008Taylor et al 2009;Guo et al 2009).…”

Metabonomic identification of novel biomarkers in doxorubicin cardiotoxicity and protective effect of the natural antioxidant oleuropein

“…This approach allows rapid analysis of the biofluid profiles of samples taking advantage of the degree of inherent biochemical similarities between samples and has been used as a powerful tool in metabonomic studies in the fields of drug toxicology and disease diagnosis (11)(12)(13)(14). NMR-based metabonomics provides an insight into the site, severity, and mechanisms of toxic damage (15)(16)(17) when applied in biofluids and tissues from animals treated with drugs and toxins, and allows simultaneous monitoring of a variety of endogenous metabolites.…”

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

“…The fact that an elevation of acetate was not observed in HgCl 2 treated kidney samples would imply that HgCl 2 may instead cause acidosis in the kidney. HgCl 2 -induced acidosis has been described previously in HgCl 2 -and cadmium-treated rats [14,22].…”

“…1 H HRMAS NMR spectroscopy has been successfully applied to study many types of tissue including liver [5,10], kidney [11] and testis [7] in rats, and a range of human tissues from healthy and diseased populations [12,13]. 1 H HRMAS approaches have also been applied to a few toxin studies in experimental animals with toxins including arsenic (As 3+ ) [8], cadmium [14,15] 2-bromoethanamine [6] and thioacetamide [16]. HgCl 2 is a potent and well-known model for induction of renal cortical toxicity and targets the S2/S3 portion of the renal proximal tubules of experimental animals [17][18][19][20].…”