Oleanolic acid 3-glucoside, a synthetic oleanane-type saponin, alleviates methylmercury toxicity in vitro and in vivo
| Autor: | Tatsuya Shirahata, Masako Kiyono, Naruki Konishi, Ryosuke Nakamura, Shimpei Uraguchi, Yuka Sone, Yoshinori Kobayashi, Yasukazu Takanezawa |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Spleen Pharmacology Toxicology Mice Random Allocation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucosides In vivo medicine Animals Humans Viability assay Oleanolic Acid Oleanolic acid Methylmercury Mice Inbred BALB C Kidney Dose-Response Relationship Drug Chemistry Methylmercury Compounds Saponins In vitro Gastrointestinal Tract 030104 developmental biology medicine.anatomical_structure Toxicity Caco-2 Cells 030217 neurology & neurosurgery |
| Zdroj: | Toxicology. 417:15-22 |
| ISSN: | 0300-483X |
| Popis: | Methylmercury (MeHg) is one of the most toxic environmental pollutants, presenting a serious health hazard worldwide. In this study, we examined the potential of derivatives of oleanolic acid (OA), such as OA 3-glucoside, OA 28-glucoside, and OA 3,28-diglucoside, to mitigate MeHg toxicity in vitro and in vivo. We found that OA 3-glucoside suppressed the cellular MeHg uptake by 63.4% compared with that of the control and improved the cell viability from 75.4% to 107.9% upon exposure to cytotoxic MeHg in Caco-2 cells. To verify the anti-MeHg activity of OA 3-glucoside, mice were orally administered MeHg (0, 1.0, or 5.0 mg kg−1·d−1), with or without OA 3-glucoside, and then mercury accumulation was measured in various organs of the mice. The mice co-treated with MeHg and OA 3-glucoside showed significantly lower mercury content in organs such as the cerebrum, cerebellum, liver, kidney, and spleen, with 83.1%, 68.7%, 71.7%, 82.1%, and 18.2% of those in the OA 3-glucoside-untreated group, respectively. This suggested OA 3-glucoside had the potential as an anti-MeHg compound, owing to its ability to suppress the distribution of MeHg into organs. Supporting this hypothesis, the mice treated with MeHg and OA 3-glucoside showed a tendency to survive one day longer than the control mice. Our findings suggest OA 3-glucoside administration alleviates the toxicity of MeHg by suppressing MeHg accumulation in organs. |
| Databáze: | OpenAIRE |
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