RESUMEN
Heavy metals are the metal compounds found in earth's crust and have densities higher than that of water. Common heavy metals include the lead, arsenic, mercury, cadmium, copper, manganese, chromium, nickel, and aluminum. Their environmental levels are consistently rising above the permissible limits and they are highly toxic as enter living systems via inhalation, ingestion, or inoculation. Prolonged exposures cause the disruption of metabolism, altered gene and/or protein expression, and dysregulated metabolite profiles. Metabolomics is a state of the art analytical tool widely used for pathomolecular inv22estigations, biomarkers, drug discovery and validation of biotransformation pathways in the fields of biomedicine, nutrition, agriculture, and industry. Here, we overview studies using metabolomics as a dynamic tool to decipher the mechanisms of metabolic impairment related to heavy metal toxicities caused by the environmental or experimental exposures in different living systems. These investigations highlight the key role of metabolomics in identifying perturbations in pathways of lipid and amino acid metabolism, with a critical role of oxidative stress in metabolic impairment. We present the conclusions with future perspectives on metabolomics applications in meeting emerging needs.
RESUMEN
Exposure to Pb is widely spreading and has far-reaching negative effects on living systems. This study aimed to investigate the toxic effects of Pb, through biochemical profiling and the ameliorative effects of quercetin against Pb-toxicity. Twenty-five male Wistar albino mice were divided into the following five groups. The CON-group received normal saline; the Pb-group received PbAc; the Pb + Q-CRN group received lead acetate followed by quercetin; the Q-CRN group received quercetin; and the CRN group received corn oil. After 4 weeks, the mice were euthanized. It was speculated that Pb significantly increased the levels of serine, threonine, and asparagine and decreased the levels of valine, lysine, and glutamic acid in the plasma of Pb-group, thus impairing amino acid metabolism. However, in the Pb + Q-CRN group, the level of these six amino acids was restored significantly due to the ameliorative effect of quercetin. The presence of lipid metabolites (L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine) in mice serum was confirmed by ESI/MS. The GPx, SOD, GSH, and CAT levels were significantly decreased, and the MDA level was significantly increased, thus confirming the oxidative stress and lipid peroxidation in the Pb group. The antioxidant effect of quercetin was elucidated in the Pb + Q-CRN group. Expression of CPT-I, CPT-II, LCAT, CROT, CACT, and MTR genes was significantly upregulated in the liver of Pb goup mice. Hence, the findings of this study proved that Pb exposure induced oxidative stress, upregulated gene expression, and impaired the lipid and amino acid metabolism in mice.
RESUMEN
Exposure to bisphenol A (BPA) is unavoidable and it has far-reaching negative effects on living systems. This study aimed to explore the toxic effects of BPA in an experimental animal model through a metabolomics approach that is useful in measuring small molecule perturbations. Beside this, we also examined the ameliorative effects of resveratrol (RSV) against BPA-induced disturbances in experimental mice. This study was conducted for 28 days, and the results showed that BPA indeed induced an impairment in amino acid metabolism, taking place in the mitochondria by significantly (p < 0.05) decreasing the levels of certain amino acids, i.e., taurine, threonine, asparagine, leucine, norleucine, and glutamic acid in the mice plasma. However, the administration of RSV did prove effective against the BPA-induced intoxication and significantly (p < 0.05) restored the level of free amino acids. Lipid metabolites, L-carnitine, sphinganine, phytosphingosine, and lysophosphatidylcholine were also determined in the mice serum. A significant (p < 0.05) decline in glutathione peroxidase (GPx), superoxide dismutase (SOD,) glutathione, and catalase levels and an elevation in malondialdehyde level in the BPA group confirmed the generation of oxidative stress and lipid peroxidation in experimental mice exposed to BPA. The expression of Carnitine palmitoyltransferase I (CPT-I), carnitine palmitoyltransferase II (CPT-II), lecithin−cholesterol acyltransferase (LCAT), carnitine O-octanoyltransferase (CROT), carnitine-acylcarnitine translocase (CACT), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) genes was significantly upregulated in the liver tissue homogenates of experimental mice exposed to BPA, although RSV regulated the expression of these genes when compared with BPA treated experimental mice. CPT-I, CPT-II, and CACT genes are located in the mitochondria and are involved in the metabolism and transportation of carnitine. Hence, this study confirms that BPA exposure induced oxidative stress, upregulated gene expression, and impaired lipid and amino acid metabolism in experimental mice.
