In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway
Tri-(2,3-dibromopropyl) isocyanate (TBC), a newly brominated flame retardant, is widely used in the synthesis of flame retardant materials with characteristics of persistent organic pollutants. To obtain environmental exposure risks of TBC, Wistar rats and HepG2 cell were used for in vivo and in vit...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322010260 |
| _version_ | 1798046340571201536 |
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| author | Furui Han Zhiwei Le Miao Yu Zheng Qi |
| author_facet | Furui Han Zhiwei Le Miao Yu Zheng Qi |
| author_sort | Furui Han |
| collection | DOAJ |
| description | Tri-(2,3-dibromopropyl) isocyanate (TBC), a newly brominated flame retardant, is widely used in the synthesis of flame retardant materials with characteristics of persistent organic pollutants. To obtain environmental exposure risks of TBC, Wistar rats and HepG2 cell were used for in vivo and in vitro studies on the toxicity of TBC and relevant ecotoxicological mechanisms of apoptosis. 80 Wistar rats were randomly selected and divided into four exposure groups (0, 0.313, 0.625, 1.250) g/(kg·bw) TBC, half male and half female, with oral administration for 28 days. Wistar rats exhibited appetite loss, weight loss, and dull hair with increasing period of TBC exposure. The pathological examinations revealed the most severe damage of liver and the ratio of liver/body weight of 35.497 × 10-3 for high-dosed group (1.250 g/kg·bw) was higher than that of 32.792 × 10-3 for control group in female rats with identical trend in male rats. The above indicators was fairly consistent with the serum test results which further confirmed the liver to be the target organ. The exposure dosages of HepG2 cell were (0, 12.5, 25, 50) μg/mL, individually. The HepG2 cells exposed to TBC for 72 h displayed hazy cell contour and decreased density of cell growth. And there was an inhibition detected by MTT assay, where the maximum inhibition rate was 19.93% under the dose of 50 μg/mL TBC. Apoptosis rate detected by flow cytometry which was demonstrated to be positively correlated to exposure dosage of TBC. The apoptosis rates of the low, medium and high dose groups of TBC exposure were (1.082 ± 0.109) %, (3.017 ± 0.09) % and (6.813 ± 0.233) %, individually. Targeted genes and corresponding protein expressions that triggering apoptosis both in vivo and in vitro were significantly altered. Overall, this work discloses the impacts of TBC exposure on hepatotoxicity, which provides new insights for chemical risk assessments of accelerate cell apoptosis via mitochondrial and death receptor pathway. |
| first_indexed | 2024-04-11T23:36:14Z |
| format | Article |
| id | doaj.art-c036102558a345b0b8d5c4b0e28d006b |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T23:36:14Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-c036102558a345b0b8d5c4b0e28d006b2022-12-22T03:56:57ZengElsevierEcotoxicology and Environmental Safety0147-65132022-11-01246114186In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathwayFurui Han0Zhiwei Le1Miao Yu2Zheng Qi3Engineering Research Center for Medicine, Ministry of Education, Harbin University of Commerce, 138 Tongda Street, Daoli District, Harbin 150076, ChinaEngineering Research Center for Medicine, Ministry of Education, Harbin University of Commerce, 138 Tongda Street, Daoli District, Harbin 150076, ChinaCorresponding authors.; Engineering Research Center for Medicine, Ministry of Education, Harbin University of Commerce, 138 Tongda Street, Daoli District, Harbin 150076, ChinaCorresponding authors.; Engineering Research Center for Medicine, Ministry of Education, Harbin University of Commerce, 138 Tongda Street, Daoli District, Harbin 150076, ChinaTri-(2,3-dibromopropyl) isocyanate (TBC), a newly brominated flame retardant, is widely used in the synthesis of flame retardant materials with characteristics of persistent organic pollutants. To obtain environmental exposure risks of TBC, Wistar rats and HepG2 cell were used for in vivo and in vitro studies on the toxicity of TBC and relevant ecotoxicological mechanisms of apoptosis. 80 Wistar rats were randomly selected and divided into four exposure groups (0, 0.313, 0.625, 1.250) g/(kg·bw) TBC, half male and half female, with oral administration for 28 days. Wistar rats exhibited appetite loss, weight loss, and dull hair with increasing period of TBC exposure. The pathological examinations revealed the most severe damage of liver and the ratio of liver/body weight of 35.497 × 10-3 for high-dosed group (1.250 g/kg·bw) was higher than that of 32.792 × 10-3 for control group in female rats with identical trend in male rats. The above indicators was fairly consistent with the serum test results which further confirmed the liver to be the target organ. The exposure dosages of HepG2 cell were (0, 12.5, 25, 50) μg/mL, individually. The HepG2 cells exposed to TBC for 72 h displayed hazy cell contour and decreased density of cell growth. And there was an inhibition detected by MTT assay, where the maximum inhibition rate was 19.93% under the dose of 50 μg/mL TBC. Apoptosis rate detected by flow cytometry which was demonstrated to be positively correlated to exposure dosage of TBC. The apoptosis rates of the low, medium and high dose groups of TBC exposure were (1.082 ± 0.109) %, (3.017 ± 0.09) % and (6.813 ± 0.233) %, individually. Targeted genes and corresponding protein expressions that triggering apoptosis both in vivo and in vitro were significantly altered. Overall, this work discloses the impacts of TBC exposure on hepatotoxicity, which provides new insights for chemical risk assessments of accelerate cell apoptosis via mitochondrial and death receptor pathway.http://www.sciencedirect.com/science/article/pii/S0147651322010260Brominated flame retardantEcotoxicologyHepatotoxicitySignal pathway |
| spellingShingle | Furui Han Zhiwei Le Miao Yu Zheng Qi In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway Ecotoxicology and Environmental Safety Brominated flame retardant Ecotoxicology Hepatotoxicity Signal pathway |
| title | In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway |
| title_full | In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway |
| title_fullStr | In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway |
| title_full_unstemmed | In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway |
| title_short | In vivo and in vitro study on hepatotoxicity of Tris-(2, 3-dibromopropyl) isocyanurate exposure via mitochondrial and death receptor pathway |
| title_sort | in vivo and in vitro study on hepatotoxicity of tris 2 3 dibromopropyl isocyanurate exposure via mitochondrial and death receptor pathway |
| topic | Brominated flame retardant Ecotoxicology Hepatotoxicity Signal pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322010260 |
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