Metabolic Impairments Caused by a “Chemical Cocktail” of DDE and Selenium in Mice Using Direct Infusion Triple Quadrupole Time-of-Flight and Gas Chromatography–Mass Spectrometry

Abstract

Among the organic contaminants, pesticides are one of the most important groups of chemicals due to their persistent character and toxicity. However, the biological systems are exposed to a complex environment in which the contaminants can interact in a synergistic/antagonistic fashion and for this reason; the study of "chemical cocktails" is of great interest to fully understand the final biological effect. In this way, selenium is known for its antagonistic action against several toxicants. In this paper, the metabolic impairments caused by the joint exposure of p,p´-dichloro diphenyl trichloroethane (DDE) and selenium (Se) have been issued for the first time. A metabolomic workflow was applied to mice fed DDE and DDE with Se diet, on the basis of the complementary use of two organic mass spectrometric techniques, combining direct infusion mass spectrometry (DI-ESI-QqQ-TOF MS) and gas chromatography mass spectrometry (GC-MS). The results show a good classification between the studied groups caused by about 70 altered metabolites in liver, kidney or brain, including the pathways of energy metabolism, degradation of phospholipidic membrane, β-oxidation and oxidative stress, which confirm the potential of combined metabolomic platforms in environmental studies.

Pesticides Exposure-Induced Changes in Brain Metabolome: Implications in the Pathogenesis of Neurodegenerative Disorders

“…Amino acids are building blocks for several other metabolic pathways, including neurotransmitter synthesis as well as purine and pyrimidine synthesis, and thus alterations in their levels can impair other necessary pathways within the brain (Rose 2019). Exposure to p,p'-dichloro-diphenyl-trichloroethane (DDE) led to an increase in the glutamine levels and metabolism of glu-tamate, aspartate, and alanine in the brain (Rodríguez-Moro et al 2019). This pathway is the major regulator of glutamate levels and the maintenance of the homeostasis of glutamate levels through the subsequent conversion into γ-aminobutyrate (GABA), one of the main inhibitory neurotransmitters (Pardo et al 2011).…”

“…Increased glutamine also finds its use in the purine and pyrimidine biosynthesis, Krebs, and urea cycle (Cruzat et al 2018 ). Furthermore, proline, which has a prominent role in scavenging reactive oxygen species (Liang et al 2013 ), was found to increase, which may indicate oxidative stress in the cell (Rodríguez-Moro et al 2019 ). A group of pregnant rats exposed to a mixture of pesticides showed decreased levels of amino acids like glutamine, serine, lysine, and ethanolamine in the brain, indicating altered the amino acid metabolites (Bonvallot et al 2018 ).…”

Analysis of Indirect Biomarkers of Effect after Exposure to Low Doses of Bisphenol A in a Study of Successive Generations of Mice

“…On another level, multigenerational studies evaluating blood biochemistry after exposure to BPA are very rare [70,71]. Finally, a future line of research could be the exposure to cocktails of emerging pollutants [72], which could exert an additive or synergic effect, and could give rise to new risk reassessments.…”

Metabolic Impairments Caused by Pesticides in Mammals and Their Interactions with Other Pollutants

“…Moreover, the chemical form or specie of selenium is very important since the essentiality or toxicity is directly related to that. Likewise, some of them, especially selenoproteins are peroxidases or oxidoreductases, which protect against oxidative stress [21][22][23][24]26], while inorganic selenium is toxic at high levels [14]. Our research group has been working with Mus musculus mice exposed to the pesticide dichlorodiphenyldichloroethylene (DDE) and selenium [27] to study the join effect in the metabolome, as well as several exposure experiments to one or two metals (metalloids) in Mus musculus like Se-Cd [2], Hg-Se [28] and others.…”