Abstract
The growing number of studies on metallothioneins (MTs), cysteine-rich metal-binding proteins, have been disclosing new functions of these proteins. Thanks to their inducibility, they were considered to play a pivotal role in regulating trace metals homeostasis and in detoxification from heavy metals; nowadays, it is known that they are involved in various physiological and pathological processes, such as regulation of apoptosis, elimination of free radicals, and protection of nucleic acids against toxic insults. MT induction has been demonstrated following stress factors other than heavy metals, such as endocrine-disrupting chemicals, insecticides, and herbicides. However, retrieved data are often controversial: in some cases, xenobiotics elicit MT expression and synthesis; under different conditions, they lead to a decrease in cellular MT content. This review describes the MT response to dichlorodiphenyltrichloroethane (DDT) contamination in mammalian tissues. In particular, attention focuses on changes in MT expression, synthesis, and localization in rat liver, kidneys, and testes following oral administration of dichlorodiphenyldichloroethylene (DDE), the main metabolite of DDT, under normal dietary conditions or in combination with a high fat diet potentially able to increase the cellular uptake of this lipophilic pesticide. The potential connection between MT expression and synthesis, lipophilic substances and trace metals availability is also discussed.
Highlights
Since their discovery in the equine renal cortex in 1956 [1], metallothioneins (MTs) are known especially for their detoxifying properties against toxic heavy metals [2]
Cytosolic proteins are ubiquitously expressed in almost all animal cell types [4,5]; under physiological conditions, they bind to essential metals, such as zinc (Zn) and copper (Cu), forming a reserve of these micronutrients immediately available in the cells; they exhibit high affinity for toxic heavy metals without any biological function, such as mercury (Hg), lead (Pb), and cadmium (Cd) [6]
The current review summarizes the recent knowledge of MT response to dichlorodiphenyltrichloroethane (DDT) contamination in mammalian tissues
Summary
Since their discovery in the equine renal cortex in 1956 [1], metallothioneins (MTs) are known especially for their detoxifying properties against toxic heavy metals [2]. The molecular outline of MT gene expression showed the ability of the reactive oxygen species (ROS) to induce production of the MTs, which in turn act as scavengers, reducing the toxic effect of free radicals, especially at the DNA level [22,23] For their inducibility and their involvement in cellular responses to stress factors, nowadays MTs are considered excellent biomarkers for assessing environmental pollution by heavy metals [24,25,26,27], and by many other substances of known or uncertain cellular toxicity, such as insecticides and herbicides [28,29,30,31,32,33]. The literature search up to December 2019 was performed on the electronic databases PubMed, Scopus, and Web of Science with the following search keywords: “metallothionein” AND “Dichloro–Diphenyl–Trichloroethane”, “metallothionein” AND “pesticides”
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