Potential of MALDI imaging for the toxicological evaluation of environmental pollutants

Abstract

Risk assessment related to the exposure of humans to chemicals released into the environment is a major concern of our modern societies. In this context, toxicology plays a crucial role to characterize the effects of this exposure on health and identify the targets of these molecules. MALDI imaging mass spectrometry (IMS) is an enabling technology for biodistribution studies of chemicals. Although the majority of published studies are presented in a pharmacological context, the concepts discussed in this review can be applied to the toxicological evaluation of chemicals released into the environment. The major asset of IMS is the simultaneous localization and identification of a parent molecule and its metabolites without labeling and without any prior knowledge. Quantification methods developed in IMS are presented with application to an environmental pollutant. IMS is effective in the localization of chemicals and endogenous species. This opens unique perspectives for the discovery of molecular alterations in metabolites and protein biomarkers that could help for a better understanding of toxicity mechanisms. Distribution studies of agrochemicals in plants by IMS can contribute to a better understanding of their mode of action and to a more effective use of these chemicals, avoiding the current concern of environmental damage.

Keywords: Environmental pollutants; Imaging; MALDI; Mass spectrometry; Toxicology.

Fig. 1.

Simultaneous localization of olanzapine and its metabolites at 2 h post-dose in a whole-rat sagittal tissue section by IMS. A) Optical image of the dosed rat tissue section with organs outlined in red, and MALDI images of B) olanzapine (SRM transition m/z 313 ➔ 256), C) N-desmethyl metabolite (SRM transition m/z 299 ➔ 256) and D) of 2-hydroxymethyl metabolite (SRM transition m/z 329 ➔ 272). Adapted from Khatib-Sahidi et al. [15] with permission. Copyright 2006 American Chemical Society.

Fig. 2.

Quantitative IMS of kidney tissue dosed with PMZ along with an H&E stained serial section for histological comparison. The results from IMS and HPLC-MS/MS were in agreement for the entire tissue section, and the image provides additional information about the localization of PMZ to the cortex region of the kidney. Adapted from Chumbley et al. [34] with permission. Copyright 2016 American Chemical Society.

Fig. 3.

In situ absolute quantification of chlordecone in the mouse liver by IMS. A) The quantificationmethod was calibratedwith different amounts of chlordeconemanually spotted on acontrol section and normalized with an internal standard (¹³C₁₀-chlordecone) added in the matrix solution. B) In situ absolute quantification of chlordecone in the pathological liver of achlordecone and CCl₄ treated mouse with the microscopic image of a serial section stained with H&E and the MALDI image corresponding to chlordecone hydrate: the local absolutequantities measured in each necrotic areas are lower than that measured in the healthy tissue (381 μg/g). C) Accumulation profile of chlordecone in the mouse liver after an exposureof 1, 2, 5, 10, or 25 days at 5 mg/kg bw. Adapted from Lagarrigue et al. [33] with permission. Copyright 2014 American Chemical Society.

Fig. 4.

MALDI imaging of azoxystrobin on wheat leaf after track sprayer application. Adapted from Annangudi et al. [53] with permission. Copyright 2015 American Chemical Society.