JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Ding Zhang,Ting Zhang,Jingying Liu,Jianshan Chen,Ying Li,Guanbao Ning,Nairui Huo,Wenxia Tian,Haili Ma
Cadmium (Cd) is a toxic metal leading to multiple forms of organ damage. Zinc (Zn) was reported as a potential antagonist against Cd toxicity. The present study investigates the antagonistic effect of Zn (20 μM) on Cd (20 or 50 μM) cytotoxicity in macrophages in vitro. The results shows that Cd exposure caused dose-dependent morphologic and ultrastructural alterations in RAW 264.7 macrophages. Zn supplement significantly inhibited Cd cytotoxicity in RAW 264.7 or HD-11 macrophages by mitigating cell apoptosis, excessive ROS output, and mitochondrial membrane depolarization. Notably, Zn supplement for 12 h remarkably prevented intracellular Cd2+ accumulation in 20 μM (95.99 ± 9.93 vs 29.64 ± 5.08 ng/106 cells; P = 0.0008) or 50 μM Cd (179.78 ± 28.66 vs 141.62 ± 22.15 ng/106 cells; P = 0.003) exposed RAW 264.7 cells. Further investigation found that Cd promoted metallothioneins (MTs) and metal regulatory transcription factor 1 (MTF-1) expression in RAW 264.7 macrophages. Twenty μM Zn supplement dramatically enhanced MTs and MTF-1 levels in Cd-exposed RAW 264.7 macrophages. Intracellular Zn2+ chelation or MTF-1 gene silencing inhibited MTs synthesis in Cd-exposed RAW 264.7 macrophages, which was accompanied by the declined expression of MTF-1, indicating that regulation of Zn on MTs was partially achieved by MTF-1 mobilization. In conclusion, this study demonstrates the antagonism of Zn against Cd cytotoxicity in macrophages and reveals its antagonistic mechanism by preventing Cd2+ bioaccumulation and promoting MTs expression.
研究领域:
毒理学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Beiyu Zhang,Meiling Li,Guangteng Zhou,Xin Gu,Longqiang Xie,Man Zhao,Qingbiao Xu,Gaoming Tan,Niya Zhang
Aflatoxin B 1 (AFB 1 ) is a mycotoxin widely present in animal feed and human food, posing a serious threat to animal and human health. This study was aim to illustrate the mechanism of the protective role of MT against AFB 1 -induced hepatotoxicity, as well as to explore the feasibility of enhancing the tolerance of poultry to AFB 1 by upregulating the expression of hepatic MT. After being exposed to AFB 1 (50 ng/kg) primary duckling hepatocytes, the cell viability, the antioxidant index (SOD and GPx) and the mRNA levels of MT downstream genes ( PTGR , p53 , TrxR , AR and Bcl-2 ) significantly ( p < 0.05) decreased, while the intracellular formation of (AFBO)-DNA adduct content, apoptosis, and MDA content significantly ( p < 0.05) increased. Interestingly, overexpression of MT in primary duckling hepatocytes markedly ( p < 0.05) reversed the detrimental impact of AFB 1 and increased the expression of MT downstream genes. HepG2 cells were applied to study the mechanism how MT works to relieve the hepatic toxicity of AFB 1 . The ZnO-NPs (20 μg/mL) + AFB 1 (20 μg/mL) group significantly ( p < 0.05) increased the cell viability, the expression of NRF2 , NQO1 and SOD , and expression of MT and MTF-1 , as well as significantly ( p < 0.05) decreased LDH, ROS and apoptotic rate, comparing with the AFB 1 group. While joint treatment with AFB 1 and ZnO-NPs, the hepatic toxicity exerted by AFB 1 alone was reversed, along with the translocation of MTF-1 from the cytoplasm to the nucleus and upregulated its expression. Duckling trails were further carried out. A total number of 96 1-day-old healthy Cherry Valley commercial ducklings were randomly allocated according to a 2 by 2 factorial arrangement of treatments with the main factors including oral administration of AFB 1 (0 vs. 40 μg/kg) and dietary supplementation of ZnO-NPs (0 vs. 60 mg/kg) for 7 days. It showed that AFB 1 exposure caused body weight loss ( p < 0.05), impaired liver structure and failure in hepatic function (activity of ALT, AST and concentration of TP and GLU) ( p < 0.05), and decreases in antioxidant capacity(activity of SOD, CAT and concentration of GSH) ( p < 0.05), along with the decrease in hepatic concentration of Zn, increase in expression of apoptosis-related genes and protein CAS3 and mRNA Bcl-2 expression ( p < 0.05), and suppressed mRNA levels of antioxidant-related genes MT , SOD1 , NRF2 , and NQO1 ( p < 0.05). In accordance with the cell test, dietary supplementation with ZnO-NPs mitigated the toxicity exerted by AFB 1 . In conclusion, ZnO-NPs has the protective effects against AFB 1 -induced hepatocyte injury by activating the expression of MTF-1 and the ectopic induction of MT expression, providing detailed information on the detoxification ability of MT on AFB 1 .
研究领域:
毒理学
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分子生物学
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动物科学
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兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）