Combined sodium selenite-cinnabar suppresses mercury accumulation and modulates nephrotoxic responses in mice.

Abstract

Cinnabar (ZS) is a commonly used in traditional Chinese medicine (TCM), but its clinical application is limited owing to mercury (Hg) related toxicity. This study aimed to explore the kidney toxic and related mechanisms of ZS combined with sodium selenite (Na₂SeO₃). Eighty specific-pathogen-free (SPF) male Kunming (KM) mice were randomly divided into ten groups: control (0.5% CMC-Na), HgS (50 mg·kg^- 1), ZhuShaAnShenWan (ZSASW) (600 mg·kg^- 1), Hg(NO₃)₂ (1.2 mg·kg^- 1), cinnabar-L(ZS-L) (50 mg·kg^- 1), cinnabar-H (ZS-H) (200 mg·kg^- 1), Na₂SeO₃ (1 mg·kg^- 1), ZS-Na₂SeO₃ (50 mg/kg-1 mg·kg^- 1), HgS-Na₂SeO₃ (50 mg·kg^- 1-1 mg·kg^- 1) and ZSASW-Na₂SeO₃ (600 mg·kg^- 1-1 mg·kg^- 1). All mice received intragastric administration once daily for 30 consecutive days. Kidney contents of Hg, selenium (Se) and other trace elements were measured by inductively coupled plasma-mass spectrometry (ICP-MS) and related detection instruments. Kidney histopathological lesions, cell apoptosis and serum levels of creatinine (Cre), blood urea nitrogen (BUN) and uric acid (UA) were detected to assess renal injury. The results demonstrated that the kidney cell apoptosis rate higher in Na₂SeO₃ (P < 0.05) and ZS-H groups (P < 0.05) than in ZS-L and ZS-Na₂SeO₃ combination groups. Serum kidney function indexes were obviously increased in HgS-Na₂SeO₃, Na₂SeO₃ groups compared with the control group (P < 0.05). The mercury content in the kidneys of the ZS-H group was 10.51 µg·g^- 1, ZS-L group was 7.99 µg·g^- 1, while that of the ZS-Na₂SeO₃ group was 3.43 µg·g^- 1. Inorganic mercury exhibited stronger kidney accumulation capacity than ZS and ZSASW. The toxic effect of ZS is not equivalent to that of inorganic mercury. The content of Hg in kidney was positively correlated with the dose. Co-administration of Na₂SeO₃ and ZS could lower kidney mercury accumulation. This could result from suppressed intestinal Hg absorption or formation of inert in-vivo complexes. Relevant component interactions should be fully considered when evaluating the safety and toxicity of ZS.