Selenium species-dependent toxicity, bioavailability and metabolic transformations inCaenorhabditis elegans

Abstract

The essential micronutrient selenium (Se) is required for various systemic functions, but its beneficial range is narrow and overexposure may result in adverse health effects. Additionally, the chemical form of the ingested selenium contributes crucially to its health effects. While small Se species play a major role in Se metabolism, their toxicological effects, bioavailability and metabolic transformations following elevated uptake are poorly understood. Utilizing the tractable invertebrate Caenorhabditis elegans allowed for an alternative approach to study species-specific characteristics of organic and inorganic Se forms in vivo, revealing remarkable species-dependent differences in the toxicity and bioavailability of selenite, selenomethionine (SeMet) and Se-methylselenocysteine (MeSeCys). An inverse relationship was found between toxicity and bioavailability of the Se species, with the organic species displaying a higher bioavailability than the inorganic form, yet being less toxic. Quantitative Se speciation analysis with HPLC/mass spectrometry revealed a partial metabolism of SeMet and MeSeCys. In SeMet exposed worms, identified metabolites were Se-adenosylselenomethionine (AdoSeMet) and Se-adenosylselenohomocysteine (AdoSeHcy), while worms exposed to MeSeCys produced Se-methylselenoglutathione (MeSeGSH) and γ-glutamyl-MeSeCys (γ-Glu-MeSeCys). Moreover, the possible role of the sole selenoprotein in the nematode, thioredoxin reductase-1 (TrxR-1), was studied comparing wildtype and trxr-1 deletion mutants. Although a lower basal Se level was detected in trxr-1 mutants, Se toxicity and bioavailability following acute exposure was indistinguishable from wildtype worms. Altogether, the current study demonstrates the suitability of C. elegans as a model for Se species dependent toxicity and metabolism, while further research is needed to elucidate TrxR-1 function in the nematode.

Treatment of Caenorhabditis elegans with Small Selenium Species Enhances Antioxidant Defense Systems

“…In wildtype L1 larvae, treatment with 100 µ m of the Se species during hatching resulted in 20‐ to 80‐fold increased Se levels compared to worms hatched in control buffer only. In agreement with observations from an acute high‐dose exposure study in C. elegans and studies in other models, for example, ref. , the seleno‐amino acids SeMet and MeSeCys accumulated to a greater extent than the inorganic selenite.…”

“…, the seleno‐amino acids SeMet and MeSeCys accumulated to a greater extent than the inorganic selenite. Similar Se contents were obtained for the txnrd‐1 deletion mutant strain VB1414, indicating that the bioavailability of the Se species is independent of the sole C. elegans selenoprotein, which was observed before in the high‐dose study …”

“…However, in L1 stage txnrd‐1 mutants, the amount of Se in the protein fraction was lower than in wildtype worms, which might be attributed to the lack of TXNRD‐1. Overall, txnrd‐1 worms have a significantly lower Se basal level than wildtype worms . Interestingly, in L4 stage worms, the basal distribution was similar in both strains.…”

Mass Surveilance of C. elegans—Smartphone-Based DIY Microscope and Machine-Learning-Based Approach for Worm Detection

“…After 24–48 h, the worms were again screened to identify dead individuals and obtain dose–response–survival curves (Steps 3,4). In the past, screening was done using a costly microscope and by detecting live and dead animals by eye [20,21]. Since about 50 animals needed to be counted per dish, with 3 independent dishes per concentration, manual counting is very time-consuming, taking several minutes per dish.…”

HIF-1 Has a Central Role in Caenorhabditis elegans Organismal Response to Selenium

“…At the Kumar, 1992;Turner et al, 1998). However, in C. elegans neither single TRXR-1 and TRXR-2 mutants nor the double TRXR-1; TRXR-2 mutant differed in Se sensitivity from the wild type (Boehler et al, 2013;Rohn et al, 2018). Transcriptomic experiments showed that under elevated Se concentrations, the expression of oxidoreductase genes was enriched suggesting an increase in reactive oxygen species (Boehler et al, 2014).…”