Adaptive mechanisms induced by sparingly soluble mercury sulfide (HgS) in zebrafish: Behavioural and proteomics analysis

Mercury (Hg) causes great health concerns due to its extreme neurotoxicity. However, here we show that pretreatment of sparingly soluble mercury compound (HgS) could induce adaptive mechanisms in zebrafish, which can resist the neurotoxic effects of mercury chloride (HgCl₂). In this study, zebrafish were treated with HgS (in the form of 99% HgS arising from traditional Ayurvedic medicine Rasasindura (RS), chosen for its particle and crystallite sizes). This work was prompted by the traditional use of this form of HgS to treat nervous and immune-related diseases. Our investigation on zebrafish behaviour showed that RS pretreated fish group (RS-HG) was less severely affected by HgCl₂ exposure, as compared to the RS non-treated (VC-HG) group. Further, biochemical tests showed that RS pretreatment prevents alteration of reactive oxygen species (ROS), acetylcholinesterase (AChE), and cortisol as compared to the VC-HG group. Proteomics and bioinformatics studies of zebrafish brain tissues suggested that Rasasindura (RS-HG group) protects alteration of various protein expression related to KEGG pathways, including citrate cycle (TCA cycle) and glutathione metabolism that are directly or indirectly linked to the oxidative stress, against HgCl₂ induced neurotoxicity. We found that adaptive mechanisms were initiated by the initiation of response to stress (enrichment of GO:0006950 pathway), due to the accumulation of a small amount of ionic Hg (60 ± 10 ng/g) after 15 days of RS treatment. These adaptive mechanisms avoid further adverse neurotoxicity of HgCl₂. Thus, HgS (RS) pretreatment can induce protective effects in zebrafish.