The antagonistic effect of selenium (Se) on mercury (Hg) toxicity has been known for decades. Earlier studies mainly focused on Hg-Se interaction based on biokinetics and bioaccumulation, but the influences of Se on in vivo biotransformation of methylmercury (MeHg) have not been well understood. We conducted a 42-day exposure study to investigate the dynamic changes of MeHg and its primary degradation product - inorganic mercury (IHg) - in different organs of black seabream (Acanthopagrus schlegeli) exposed to different dietary Se levels. A physiologically based pharmacokinetic (PBPK) model was then developed to describe the biotransformation and disposition of MeHg under the influence of Se. Our results demonstrated that Se significantly increased the transformation from MeHg into IHg, thereby decreasing the accumulation of MeHg. The simulation further showed that the intestine was the major site for demethylation, with an estimated rate 1.5-fold higher in high Se treatment than in low Se treatment. However, the hepatic demethylation rate was extremely low and comparable between the two treatments (0.012–0.015 d⁻¹). These results strongly suggested that the intestine instead of the commonly assumed liver was the major site for Hg-Se interaction. Furthermore, Se did not show significant influences on the distribution and elimination of MeHg, but promoted the uptake and elimination of the generated IHg from demethylation. Therefore, Se-induced demethylation especially in the intestine played an important role in mitigating the MeHg accumulation. This study provided new sight to elucidate the Hg-Se interaction in fish.

硒（Se）对汞（Hg）毒性的拮抗作用已有数十年了。早期的研究主要基于生物动力学和生物蓄积性来研究汞与硒的相互作用，但是硒对甲基汞（MeHg）体内生物转化的影响尚不十分清楚。我们进行了一项为期42天的暴露研究，以研究黑鲷（Acanthopagrus schlegeli）不同器官中MeHg及其主要降解产物无机汞（IHg）的动态变化。）暴露于不同的饮食硒水平。然后建立了基于生理学的药代动力学（PBPK）模型，以描述MeHg在Se的影响下的生物转化和处置。我们的结果表明，硒显着增加了从MeHg到IHg的转化，从而减少了MeHg的积累。模拟进一步表明，肠道是去甲基化的主要部位，高硒处理的速率估计比低硒处理高1.5倍。但是，两种方法之间的肝脱甲基率极低，相当（0.012-0.015 d ^-1）。这些结果强烈表明，肠道而不是通常认为的肝脏是Hg-Se相互作用的主要部位。此外，Se对MeHg的分布和消除没有显着影响，但促进了去甲基化对生成的IHg的吸收和消除。因此，硒诱导的去甲基化，特别是在肠道中，在减轻MeHg积累中起着重要作用。这项研究为阐明鱼类中的Hg-Se相互作用提供了新的视野。