Chemical Form Matters: Differential Accumulation of Mercury Following Inorganic and Organic Mercury Exposures in Zebrafish Larvae

Abstract

Mercury, one of the most toxic elements, exists in various chemical forms each with different toxicities and health implications. Some methylated mercury forms, one of which exists in fish and other seafood products, pose a potential threat, especially during embryonic and early postnatal development. Despite global concerns, little is known about the mechanisms underlying transport and toxicity of different mercury species. To investigate the impact of different mercury chemical forms on vertebrate development, we have successfully combined the zebrafish, a well-established developmental biology model system, with synchrotron-based X-ray fluorescence imaging. Our work revealed substantial differences in tissue-specific accumulation patterns of mercury in zebrafish larvae exposed to four different mercury formulations in water. Methylmercury species not only resulted in overall higher mercury burdens but also targeted different cells and tissues than their inorganic counterparts, thus revealing a significant role of speciation in cellular and molecular targeting and mercury sequestration. For methylmercury species, the highest mercury concentrations were in the eye lens epithelial cells, independent of the formulation ligand (chloride versusl-cysteine). For inorganic mercury species, in absence of l-cysteine, the olfactory epithelium and kidney accumulated the greatest amounts of mercury. However, with l-cysteine present in the treatment solution, mercuric bis-l-cysteineate species dominated the treatment, significantly decreasing uptake. Our results clearly demonstrate that the common differentiation between organic and inorganic mercury is not sufficient to determine the toxicity of various mercury species.

Phenylthiourea alters toxicity of mercury compounds in zebrafish larvae

“…After a 48 hour exposure all fish were rinsed 3 times in fresh system water to remove excess mercury on the surface of the fish. Zebrafish were fixed, embedded and sectioned as previously described [7].…”

“…Data collected from X-ray fluorescence imaging were processed as previously described [7], with normalization to the incoming beam intensity and removal of background signal by averaging the intensity per element in the area outside of the tissue then subtracting this amount from each pixel in the entire image. Certified highly-uniform thin film standards mounted on 6.3 μm Mylar substrates for zinc, gold, and thallium were obtained from Micromatter Co. (Vancouver, BC).…”

“…Key characteristics that make the zebrafish an excellent model vertebrate system include nearly transparent embryos, rapid development outside the mother, large egg clutch, and a fully sequenced genome [2]. As a model vertebrate system for studying the development of the embryo, researchers have used zebrafish to explore metal toxicity [2][3][4][5][6][7][8] as well as various human diseases [1,9].…”

Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug resistance-associated protein 2 (Mrp2) with furosemide

“…It has been reported that high levels of mercury exposure may occur via the use of skin lightening beauty creams, soaps and herbal drugs 3,4 . The toxic effects of mercury vary with the different chemical forms of mercury, the dose and the rate of exposure 2,5 .…”

Methods and recent advances in speciation analysis of mercury chemical species in environmental samples: a review

“…[6] For all toxic heavy metals, which undergo physical and/or chemical transformations, the total concentration of an element in general cannot reflect the hazard or benefit of their individual species. Korbas et al [7] studied the difference in toxicity between OrgHg and inorganic Hg species towards Zebrafish larvae and demonstrated that OrgHg resulted in overall higher Hg burdens and also targeted different cells and tissues than their inorganic counterparts. This indicates that the toxicity depends on the chemical forms of an element than its total quantity.…”