RESUMEN
Methylmercury (MeHg) is a ubiquitous environmental contaminant, well known for its neurotoxic effects. MeHg can interact with several nutrients in the diet and affect nutrient metabolism, however the interaction between MeHg and dietary proteins has not been thoroughly investigated. Male BALB/c mice were fed diets based on either casein, cod or chicken as protein sources, which were or were not spiked with MeHg (3.5 mg Hg kg-1). Following 13 weeks of dietary exposure to MeHg, the animals accumulated mercury in a varying degree depending on the diet, where the levels of mercury were highest in the mice fed casein and MeHg, lower in mice fed cod and MeHg, and lowest in mice fed chicken and MeHg in all tissues assessed. Assessment of gut microbiota revealed differences in microbiota composition based on the different protein sources. However, the introduction of MeHg eliminated this difference. Proteomic profiling of liver tissue uncovered the influence of the dietary protein sources on a range of enzymes related to Phase I and Phase II detoxification mechanisms, suggesting an impact of the diet on MeHg metabolism and excretion. Also, enzymes linked to pathways including methionine and glycine betaine cycling, which in turn impact the production of glutathione, an important MeHg conjugation molecule, were up-regulated in mice fed chicken as dietary protein. Our findings indicate that dietary proteins can affect expression of hepatic enzymes that potentially influence MeHg metabolism and excretion, highlighting the relevance of considering the dietary composition in risk assessment of MeHg through dietary exposure.
Asunto(s)
Proteínas en la Dieta , Hígado , Compuestos de Metilmercurio , Ratones Endogámicos BALB C , Animales , Compuestos de Metilmercurio/metabolismo , Masculino , Hígado/metabolismo , Hígado/efectos de los fármacos , Proteínas en la Dieta/metabolismo , Mercurio/metabolismo , Ratones , Pollos , Microbioma Gastrointestinal/efectos de los fármacos , Exposición Dietética/efectos adversos , DietaRESUMEN
Methylmercury (MeHg) is a well-known environmental contaminant, particularly harmful to the developing brain. The main human dietary exposure to MeHg occurs through seafood consumption. However, seafood also contains several nutrients, including selenium, which has been shown to interact with MeHg and potentially ameliorate its toxicity. The aim of this study was to investigate the combined effects of selenium (as selenomethionine; SeMet) and MeHg on mercury accumulation in tissues and the effects concomitant dietary exposure of these compounds exert on the hippocampal proteome and transcriptome in mice. Adolescent male BALB/c mice were exposed to SeMet and two different doses of MeHg through their diet for 11 weeks. Organs, including the brain, were sampled for mercury analyses. Hippocampi were collected and analyzed using proteomics and transcriptomics followed by multi-omics bioinformatics data analysis. The dietary presence of SeMet reduced the amount of mercury in several organs, including the brain. Proteomic and RNA-seq analyses showed that both protein and RNA expression patterns were inversely regulated in mice receiving SeMet together with MeHg compared to MeHg alone. Several pathways, proteins and RNA transcripts involved in conditions such as immune responses and inflammation, oxidative stress, cell plasticity and Alzheimer's disease were affected inversely by SeMet and MeHg, indicating that SeMet can ameliorate several toxic effects of MeHg in mice.
Asunto(s)
Mercurio , Compuestos de Metilmercurio , Selenio , Masculino , Adolescente , Animales , Humanos , Ratones , Compuestos de Metilmercurio/toxicidad , Compuestos de Metilmercurio/análisis , Selenometionina/farmacología , Transcriptoma , Selenio/metabolismo , Proteoma/metabolismo , Proteómica , Ratones Endogámicos BALB C , Dieta , Antioxidantes , Hipocampo/metabolismo , ARNRESUMEN
Methylmercury (MeHg) is a highly neurotoxic form of mercury (Hg) present in seafood. Here, we recorded and compared proteomic and transcriptomic changes in hippocampus of male BALB/c mice exposed to two doses of MeHg. Mice were fed diets spiked with 0.28 mg MeHg kg-1, 5 mg MeHg kg-1, or an unspiked control diet for 77 days. Total mercury content was significantly (P < 0.05) increased in brain tissue of both MeHg-exposed groups (18 ± 2 mg Hg kg-1 and 0.56 ± 0.06 mg Hg kg-1). Hippocampal protein and ribonucleic acid (RNA) expression levels were significantly altered both in tissues from mice receiving a low dose MeHg (20 proteins/294 RNA transcripts) and a high dose MeHg (61 proteins/876 RNA transcripts). The majority but not all the differentially expressed features in hippocampus were dose dependent. The combined use of transcriptomic and proteomic profiling data provided insight on the influence of MeHg on neurotoxicity, energy metabolism, and oxidative stress through several regulated features and pathways, including RXR function and superoxide radical degradation.