High-resolution magic angle spinning¹H-NMR spectroscopy studies on the renal biochemistry in the bank vole (Clethrionomys glareolus) and the effects of arsenic (As³⁺) toxicity

Abstract

1. High-resolution magic angle spinning (MAS) 1H-NMR spectroscopy was used to study renal metabolism and the toxicity of As3+, a common environmental contaminant, in the bank vole (Clethrionomys glareolus), a wild species of rodent. 2. Following a 14-day exposure to an environmentally relevant dose of As2O3 (28 mg kg(-1) feed), voles displayed tissue damage at autopsy. MAS 1H spectra indicated abnormal lipid profiles in these samples. 3. Tissue necrosis was also evident from measurements of the apparent diffusion coefficient of water in the intact tissue using MAS 1H diffusion-weighted spectroscopy, its first application to toxicology. 4. Comparison of renal tissue from the wood mouse (Apodemus sylvaticus) exposed to identical exposure levels of As3+ suggested that the bank vole is particularly vulnerable to As3+ toxicity.

A combination of metallomics and metabolomics studies to evaluate the effects of metal interactions in mammals. Application to Mus musculus mice under arsenic/cadmium exposure

“…[31] and rats under 587 cadmium exposure [32]. Increased biosynthesis of triglycerides 588 and diacylglycerol has also been found in apoptotic KB cells [33].…”

Metabolomics: Methodologies and applications in the environmental sciences

“…Terrestrial mammals such as the bank vole (Clethrionomys glareolus) have been used to study renal metabolism and the toxicity of arsenic (As 3ϩ ). 15) Magic angle spinning 1 H NMR on the intact renal tissues revealed abnormal lipid profiles and tissue necrosis leading to changes in the water diffusion coefficient in animals exposed to As 3ϩ . In contrast, the wood mouse (Apodemus sylvaticus) is less susceptible to As 3ϩ toxicity.…”

“…Even though NMR is not as sensitive as MS, it is potentially fully quantitative using a single internal standard, is extremely reproducible, employs a highly non-selective detector (metabolite requires a non-exchangeable H atom), and is able to analyze liquid and solid samples directly. In addition, NMR can be used to detect the isotopes of many elements, including 13 C, 31 P, and 15 N. For instance, biological systems can be exposed to low molecular weight substrates labelled with either 13 C or 15 N, and the metabolic pathways examined via either 13 C or 15 N NMR. 36) This approach would provide not only pathway information, but would also allow for monitoring metabolic changes over time and space.…”

“…37,41,42) With this technique, metabolite changes could be localized and further used to study tissue or site-specific mechanisms of toxicity. 15,43) The main disadvantage of NMR is its relative insensitivity. However, the use of cryogenically cooled probes and capillary probes has shown considerable promise for increasing sensitivity.…”

“…Moreover, this approach can generate information from in vivo samples to expand our understanding of the responsible toxicological or pathological mechanisms. 15) The metabolomic approach focuses on those metabolites whose levels are altered after stress. It tries to avoid biases against the observation of certain classes of metabolites, based on chemical structure or abundance in biological systems.…”