Approaches to Formaldehyde Measurement: From Liquid Biological Samples to Cells and Organisms

Abstract

Formaldehyde (FA) is the simplest aldehyde present both in the environment and in living organisms. FA is an extremely reactive compound capable of protein crosslinking and DNA damage. For a long time, FA was considered a “biochemical waste” and a by-product of normal cellular metabolism, but in recent decades the picture has changed. As a result, the need arose for novel instruments and approaches to monitor and measure not only environmental FA in water, cosmetics, and household products, but also in food, beverages and biological samples including cells and even organisms. Despite numerous protocols being developed for in vitro and in cellulo FA assessment, many of them have remained at the “proof-of-concept” stage. We analyze the suitability of different methods developed for non-biological objects, and present an overview of the recently developed approaches, including chemically-synthesized probes and genetically encoded FA-sensors for in cellulo and in vivo FA monitoring. We also discuss the prospects of classical methods such as chromatography and spectrophotometry, and how they have been adapted in response to the demand for precise, selective and highly sensitive evaluation of FA concentration fluctuations in biological samples. The main objectives of this review is to summarize data on the main approaches for FA content measurement in liquid biological samples, pointing out the advantages and disadvantages of each method; to report the progress in development of novel molecules suitable for application in living systems; and, finally, to discuss genetically encoded FA-sensors based on existing natural biological FA-responsive elements.

The Importance of Tracking “Missing” Metabolites: How and Why?

“…Nevertheless, the derivatization can be highly effective in liver microsomal incubation mixtures. 11 Similarly, volatile formaldehyde can be analyzed via GC-MS and can also be derivatized by hydrazines to be monitored and analyzed via LC-MS. 168,169 Unexpected reactive and transient metabolites from bioactivation that are quenched by endogenous small molecules and protein nucleophiles can sometimes be overlooked because the resulting metabolite structure is too large or very different from the parent molecule. Thus, trapping reagents such as GSH (for trapping epoxide, α,βunsaturated carbonyls, and other soft electrophiles), cyanide (for trapping iminium ions), semicarbazide/methoxyamine (for trapping aldehydes and migrated acyl glucuronides), and nucleobases (for epoxide, quinone and aldehyde metabolites) can provide additional data to help elucidate the sites and mechanisms of bioactivation.…”

“…Nevertheless, the derivatization can be highly effective in liver microsomal incubation mixtures . Similarly, volatile formaldehyde can be analyzed via GC-MS and can also be derivatized by hydrazines to be monitored and analyzed via LC-MS. , …”

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“…Formaldehyde imbalances have been linked to many diseases including cancer and neurodegenerative diseases (Nadalutti, Prasad, & Wilson, 2021). Formaldehyde monitoring in living things can lead to biochemical findings of pathological conditions characterized by elevated formaldehyde levels such as cancer levels and neurodegenerative disorders (Lipskerov, Sheshukova, & Komarova, 2022).…”

Reversible Near-Infrared Fluorescent Probe for Rapid Sensing Sulfur Dioxide and Formaldehyde: Recognition and Photoactivation Mechanism and Applications in Bioimaging and Encryption Ink

“…12−14 Exposure to formaldehyde increases the risk of acute poisoning, while long-term exposure can cause chronic toxicity and even cancer. 15,16 Meanwhile, as a reactive carbonyl species (RCS), formaldehyde is related to various physiological and pathological processes of organisms. 17,18 For example, it is involved in the demethylation and the methylation cycle of DNA, which is a key step in memory formation.…”

“…Furthermore, formaldehyde (HCHO) is the third major indoor chemical pollutant. − Exposure to formaldehyde increases the risk of acute poisoning, while long-term exposure can cause chronic toxicity and even cancer. , Meanwhile, as a reactive carbonyl species (RCS), formaldehyde is related to various physiological and pathological processes of organisms. , For example, it is involved in the demethylation and the methylation cycle of DNA, which is a key step in memory formation. Therefore, the detection of formaldehyde in organisms is of great significance to explore its related processes. , …”