Ayurvedic processing of α-HgS gives novel physicochemistry and distinct toxicokinetics in zebrafish

Rasasindura (RS) is an Ayurvedic medicine, which contains ∼99% α-HgS. It is used as a rejuvenating agent and commonly used to treat diseases such as syphilis, insomnia, high fever, and nervous disorders. Cinnabar ore (α-HgS) is a well-known mineral, which is readily available. Despite it, Ayurvedic practitioners adopted an involved and tedious procedure for the preparation of RS. In this study, three samples, one was Ayurvedic (RS), the second one was the commercial (HGS), and the third one was cinnabar ore (CN), were physiochemically examined. Zebrafish model was employed for toxicity study with an oral dose of 100 mg/kg/day for the three samples for 10 days. We found that RS conferred novel physicochemical properties, which were not seen in HGS and CN. Significantly, the average crystallite size of RS was lowest (26 nm) as compared to HGS (31 nm) and CN (34 nm), and the rate of increase of crystallite size with temperature was lowest in RS. RS did not show any significant behavioral toxicity in zebrafish, which was seen with the HGS-and CN-treated zebrafish. HGS-and CN-treated zebrafish showed a significantly high (∗∗∗p < 0.001) decrease (77 ± 7.6% and 51 ± 6.5%, respectively) of glutathione (GSH) levels in the brain, however, for RS-treated zebrafish, the change of GSH was insignificant (26 ± 2.5%, p > 0.05). Interestingly, HGS significantly altered the γ-aminobutyric acid (GABA) in brain tissue. Therefore, among all three samples, RS exhibited the lowest toxicity, which can be credited to the distinct toxicokinetics by these samples.