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.

Surface‐assisted laser desorption/ionization mass spectrometry imaging: A review

“…While countless samples have already been studied by MALDI-MSI in disciplines as varied as pharmaceutical research (Schulz et al, 2019;Swales et al, 2019), ecotoxicology (Lagarrigue et al, 2016), plant biology (Boughton et al, 2016), biomedicine (Schwamborn et al, 2017), and molecular biology (Cornett et al, 2007), the variety of samples that have already been imaged by SALDI-MSI remains rather limited, as shown in Figure 7 and Table 3. Among these samples, the majority of reported SALDI-MS imaging analyses focused on murine tissue sections (about 50% of which were mouse brain sections).…”

Three‐dimensional quantitative mass spectrometry imaging in complex system: From subcellular to whole organism

“…A growing number of pollutants were detected in our environment, including industrial chemicals, drugs, personal care products and food additives. Continuous pollutant exposure could induce various adverse effects in endocrine system, neurological system and respiratory system, making a threat to human health (Kabir et al, 2015; Kravchenko et al, 2015; Lagarrigue et al, 2016; Thompson et al, 2015). Generally, toxicological studies evaluate various adverse effects observed after the pollutants exposure at environment‐related dose levels.…”

“…On the basis of the analysis of biological fluids and tissue homogenates, the parent pollutants and its endogenous and exogenous metabolites are analyzed qualitatively and quantitatively by combing the MS‐based techniques and molecular biology assay, leading to the lack of spatial distribution information. Precise localization of targeted molecules and suborgan play a crucial role in toxicological evaluation of pollutants and discovery of new toxicological mechanisms (Lagarrigue et al, 2016). Lagarrigue et al (2014) described the quantification of chlordecone and investigated its accumulation in mouse liver by combing the normalization approach of internal standard and MSI analysis.…”

“…More precisely, its applications can estimate whether the targeted compounds cause toxicity and whether the compounds are accumulated in the targeted organs (Bodzon‐Kulakowska & Suder, 2016; Buchberger et al, 2018). Another feature of 3D‐MSI is related to the high‐throughput that allows the hundreds or thousands of biomolecules to be identified and localized in one experiment including the metals, metabolites, lipids, drugs, environmental pollutants, peptides, and proteins from endogenous to exogenous metabolic pathway (Bodzon‐Kulakowska & Suder, 2016; Lagarrigue et al, 2016; Buchberger et al, 2018). 3D‐MSI is also highlighted by its wide coverages from subcellular level, 3D cell spheroid, organs, to whole‐body (Liu & Hummon, 2015).…”

Regulatory Forum Opinion Piece*: Imaging Applications in Toxicologic Pathology—Recommendations for Use in Regulated Nonclinical Toxicity Studies

“…As mentioned above, targeting of the toxicity or inflammation markers can also be investigated during a safety evaluation and for some pharmacologic purposes (Caughlin et al 2015; Lagarrigue, Caprioli, and Pineau 2016; Meistermann et al 2006). For example, lipofuscin is found as spherical particles in the retinal pigment epithelium (RPE) and characterized by its autofluorescence when exposed to light.…”