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Mercuric sulfide (HgS) is a major component of cinnabar, which has been used as a sedative drug in China for more than 2000 years. Because its toxicological effects are still unclear, we attempted to verify the toxic effects of HgS, focused on liver and immune organs such as the spleen and thymus. Male ICR mice were administered HgS (0.02, 0.2, 2.0 g/kg/day) by gavage for 4 weeks. During the administration period, HgS-treated mice did not reveal overt signs of clinical toxicity. HgS had no significant effect on body weight, food consumption, water consumption, and organ weights. In spite of its known insolubility, HgS was absorbed by the gastrointestinal tract and accumulated in the liver, spleen and thymus in a dose-dependent manner. In the biochemical and histological examination, HgS did not cause hepatotoxicity. However, HgS significantly increased both CD8+ T lymphocytes and CD4+CD8+ lymphocyte populations in the spleen without changing in the thymus. In the histological evaluation, HgS induced enlargement with marked hyperplasia and increase of lymphoid follicles in the spleen. In addition, HgS induced the gene expression of pro-inflammatory cytokines in the spleen and thymus. Our results suggest that insoluble HgS was absorbed by the gastrointestinal tract, accumulated in the spleen and thymus, and thus could affect immune systems. [ABSTRACT FROM AUTHOR]

Aim: Venadaparib is a next-generation poly(ADP-ribose) polymerase inhibitor under development for treating gastric cancer. This study aimed to evaluate the effects of food and ethnicity on the pharmacokinetics (PKs) and safety of venadaparib after a single oral administration in healthy Korean, Caucasian, and Chinese male subjects., Methods: In this randomized, open-label, single-dose, two-sequence, two-period, and crossover study, Korean and Caucasian subjects received venadaparib 80 mg in each period (fasted or fed state) with a seven-day washout. In an open-label, single-dose study, Chinese subjects received venadaparib 80 mg only in the fasted state. Serial blood samples were collected up to 72 h post-dosing., Results: Twelve subjects from each ethnic group completed the study. The geometric mean ratios (90% confidence intervals) of the maximum plasma concentration (C max ) and area under the plasma concentration-time curve from time zero to the last measurable time point (AUC last ) of venadaparib for the fed to fasted state were 0.82 (0.7457-0.9094) and 1.02 (0.9088-1.1339) in Koreans, and 0.77 (0.6871-0.8609) and 0.96 (0.9017-1.0186) in Caucasians, respectively. No statistically significant differences were observed in C max (P-value = 0.45) or AUC last (P-value = 0.30) among the three ethnic groups. A single venadaparib dose was well-tolerated., Conclusion: The overall systemic exposure of venadaparib was not affected by the high-fat meal, despite delayed absorption with a decreased C max in the fed state. The PK profiles were comparable among the Korean, Caucasian, and Chinese subjects. A single venadaparib 80 mg dose was safe and well-tolerated in both fasted and fed states., (© 2023. The Author(s).)