Review: Reactive selenium metabolites as targets of toxic metals/metalloids in mammals: a molecular toxicological perspective

Abstract

Human activities have been contaminating the environment with toxic heavy metal and metalloid compounds. Since the toxicity of one metal or metalloid can be dramatically modulated by the simultaneous ingestion of another, studies addressing the molecular basis of chemical interactions between toxic and essential elements are increasingly important. The intravenous injection of rabbits with selenite and arsenite or with selenite and mercuric mercury resulted in the in vivo formation of the seleno-bis (S-glutathionyl) arsinium ion, [(GS) 2 AsSe] À , or a glutathione-coated mercuric selenide, (GS) 5 (HgSe) core , in blood. The formation of these species (and the formation of a cadmium±selenium species in blood after the exposure of rats to selenite and cadmium) critically involves reactive selenite metabolites, such as GS±Se À and/or HSe À , which indicates that these physiologically important metabolites are molecular targets of ingested toxic metals and metalloids. The fate and stability of [(GS) 2 AsSe] À and (GS) 5 (HgSe) core in vivo imply that the chronic exposure of mammals to inorganic arsenic and mercury will cumulatively affect the bioavailability of selenium, which could lead to selenium deficiency. Since selenium deficiency is significantly associated with the etiology of cancer in humans, the GSH-driven in vivo formation of selenium-containing metal and metalloid species provides a likely molecular mechanism for the chronic toxicity of environmentally persistent inorganic arsenic, mercury and cadmium.

Selenium supplementation into diets containing carnosic acid, fish and rapeseed oils affects the chemical profile of whole blood in lambs

“…Similarly, the lower concentration of As (the metalloid) was observed in whole blood of lambs fed experimental diets with CA, irrespective of the presence of SeY and SeVI, as compared to control and ROFO diets. Antagonistic interactions are observed between Se-compounds and As-species in mammal tissues (Gailer, 2002).…”

“…At physiological pH, selenohydryl groups (RSeH) exist almost completely in an anionic form: [RSe-] − (unlike the sulpfhydryl group which exists almost in the protonated form: RSH). The anionic form of the selenohydryl group is a nucleophile that binds ions of metalloids and heavy metals (Gailer, 2002). So, it can be concluded that dietary SeY (group IV) more effectively stimulated the biosynthesis of metal binding Se-biomolecules in whole blood than SeVI (group V).…”

“…Se is an important component of several biologically significant macromolecules (like proteins containing Se-CyS or Se-Met) that interact in mammal tissues with a wide range of heavy metals and metalloids such as Cu, Zn, Hg, Ag, Cd, Mn, Ni, Cr or Sb (Gailer, 2002). Various mechanisms were proposed to explain the interactions between Se and these trace elements in mammal tissues.…”

“…Firstly, reactions between metal and selenide ([-Se-] 2-) lead to the in vivo formation of insoluble or stable selenides with metal ions. Secondly, Se is able to bind to a sulphydryl group of pre-existing proteins, and then the Se-group of biomolecules subsequently binds heavy metal ions (Gailer, 2002). The chemistry of Se documents that is almost 100% present as selenol in mammals' tissues.…”

Hg2+ and Cd2+ interact differently with biomimetic erythrocyte membranes

“…with potential in vivo molecular targets are needed in order to unravel all biochemical mechanisms that are involved in their toxic effects at the organ level. To this end, the vast majority of studies that have been conducted so far have focused on the individual interaction of each metal with plasma proteins (e.g., human serum albumin) (Lau and Sarkar 1979), transmembrane proteins in erythrocytes (e.g., the hexose transport protein) (Vansteveninck et al 1965), intracellular sulfhydryl compounds (e.g., L-cysteine, L-glutathione (Rabenstein 1989) and proteins) andmore recently-reactive selenium metabolites (Gailer 2002). It has been known for a long time, however, that small concentrations of toxic metals can also produce appreciable changes of surface tension and surface charge in phospholipid bilayers (Passow et al 1961) and can increase the permeability of liposomes (Nakada et al 1978).…”