FOOD AND CHEMICAL TOXICOLOGY
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2016
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IF 3.584
Chongshan Dai,Bin Li,Yan Zhou,Daowen Li,Shen Zhang,Hui Li,Xilong Xiao,Shusheng Tang
The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress , mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor –kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX , a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.
研究领域:
药理学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
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2015
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IF 1.517
Chongshan Dai,Shusheng Tang,Daowen Li,Kena Zhao,Xilong Xiao
Quinocetone (QCT), a new quinoxaline 1,4-dioxides, has been used as antimicrobial feed additive in China. Potential genotoxicity of QCT was concerned as a public health problem. This study aimed to investigate the protective effect of curcumin on QCT-induced oxidative stress and genotoxicity in human hepatocyte L02 cells. Cell viability and intracellular reactive oxygen species (ROS), biomarkers of oxidative stress including superoxide dismutase (SOD) activity and glutathione (GSH) level were measured. Meanwhile, comet assay and micronucleus assay were carried out to evaluate genotoxicity. The results showed that, compared to the control group, QCT at the concentration ranges of 2–16 μg/mL significantly decreased L02 cell viability, which was significantly attenuated with curcumin pretreatment (2.5 and 5 μM). In addition, QCT significantly increased cell oxidative stress, characterized by increases of intracellular ROS level, while decreased endogenous antioxidant biomarkers GSH level and SOD activity (all p < 0.05 or 0.01). Curcumin pretreatment significantly attenuated ROS formation, inhibited the decreases of SOD activity and GSH level. Furthermore, curcumin significantly reduced QCT-induced DNA fragments and micronuclei formation. These data suggest that curcumin could attenuate QCT-induced cytotoxicity and genotoxicity in L02 cells, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, consumption of curcumin may be a plausible way to prevent quinoxaline 1,4-dioxides-mediated oxidative stress and genotoxicity in human or animals.
研究领域:
毒理学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
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2021
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IF 2.987
Lirui Hou,Fang Liu,Chong Zhao,Lihong Fan,Hongbo Hu,Shutao Yin
Oxytetracycline (OTC) and Quinocetone (QCT) are antimicrobials, whose residues have been found in food and environment. These two are sometimes used simultaneously in livestock and aquaculture, potentially resulting in the simultaneous consumption of multi-antimicrobials by consumers. However, the combined toxic effects of this phenomenon have yet to be addressed. Since the liver is a major target of both OTC and QCT, we tested their hepatotoxic effect using both cell cultures and animal models. Results showed that the QCT (5–25 μM) or OTC (20–100 μM) treatments alone caused dose-dependent reductions in cell numbers, while their combination strongly further enhanced inhibitory effects. Mechanistically, the combination enhanced the generation of reactive oxygen species (ROS) and activated mitochondrial cell death pathways. It also showed that the combination of OTC (800 mg/kg, i.g., 5d) and QCT (5000 mg/kg, i.g., 5d) resulted in significantly enhanced liver toxicity in C57BL/6N mice, the serum alanine transaminase (ALT) and aspartate transaminase (AST) were significantly increased by the OTC/QCT. These findings indicate the necessity of considering the combined toxicity of these two antimicrobials in safety assessments.
研究领域:
毒理学
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药理学
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细胞生物学
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动物科学
✓ 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）