Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves

Gao, ChangAn; Zhang, Aiqian; Lin, Yuan; Yin, Daqiang; Wang, Liansheng

doi:10.1007/s11434-009-0174-7

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…To avoid a chance correlation, the robustness of the QSAR model was tested using the Monte Carlo method. 38 The pseudo-r 2 of eq 8 and eq 9 (0.69 and 0.67, respectively) are much lower that their r 2 values (0.79 and 0.76, respectively), which suggests a high prediction capacity for the QSAR model. Therefore, eq 8 and eq 9 were further used for mechanistic discussion.…”

Section: ■ Resultsmentioning

confidence: 93%

“…Eqs and were obtained by coercive regression, which suggests that there is no significant correlation between −log(EC S ) and E b DHPS , or between −log(EC S ) and E b CRP . To avoid a chance correlation, the robustness of the QSAR model was tested using the Monte Carlo method . The pseudo- r 2 of eq and eq (0.69 and 0.67, respectively) are much lower that their r 2 values (0.79 and 0.76, respectively), which suggests a high prediction capacity for the QSAR model.…”

Section: Advantages Of the New Parametersmentioning

confidence: 99%

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Model of Hormesis and Its Toxicity Mechanism Based on Quorum Sensing: A Case Study on the Toxicity of Sulfonamides to Photobacterium phosphoreum

Deng

Zhao

Zou

et al. 2012

Environ. Sci. Technol.

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During the past two decades, the phenomenon of hormesis has gained increasing recognition in environmental and toxicological communities. However, the mechanistic understanding of hormesis, to date, is extremely limited. Herein is proposed a novel parametric model with a mechanistic basis and two model-based parameters for hormesis that was successfully applied to the hormetic dose-response observed in the chronic toxicity of sulfonamides on Photobacterium phosphoreum. On the basis of the methods of molecular docking and quantitative structure-activity relationships (QSARs), we proposed a mechanistic hypothesis for hormesis that introduces for the first time the concept of quorum sensing in toxicological studies and explains the mechanism at the level of the receptors. The mechanistic hypothesis stated that (1) specific target binding like interaction with LuxR may contribute to transcriptional activation leading to enhanced luciferase activity at low dose exposure of sulfonamides, and (2) as the dose of sulfonamides increases, more sulfonamides competitively bind to dihydropteroate synthase, which inhibit the biosynthesis of folic acid and thus provoke toxicity. This mechanistic hypothesis, which explains both the dose-dependent and time-dependent features of hormesis, could give new insight into the mechanistic study of hormesis.

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Section: ■ Resultsmentioning

confidence: 93%

Section: Advantages Of the New Parametersmentioning

confidence: 99%

Model of Hormesis and Its Toxicity Mechanism Based on Quorum Sensing: A Case Study on the Toxicity of Sulfonamides to Photobacterium phosphoreum

Deng

Zhao

Zou

et al. 2012

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the curve for SOD is an inverted U shape, which is better modeled by a quadratic function. Nonmonotonic curves can be attributed to diverse biological reactions that are initiated in different dose ranges , such as ROS promotion/inhibition and binding effect. The nonmonotonic behavior is worth noting because a measured low response in the biomarker result may indicate not only a lack of toxic response but also severe stress to the organism.…”

Section: Resultsmentioning

confidence: 99%

Oxidative toxicity of perfluorinated chemicals in green mussel and bioaccumulation factor dependent quantitative structure–activity relationship

Liu

Chang

Gin

2014

Enviro Toxic and Chemistry

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Concerns regarding perfluorinated chemicals (PFCs) have risen in recent years because of their ubiquitous presence and high persistency. However, data on the environmental impacts of PFCs on marine organisms are very limited. Oxidative toxicity has been suggested to be one of the major toxic pathways for PFCs to induce adverse effects on organisms. To investigate PFC-induced oxidative stress and oxidative toxicity, a series of antioxidant enzyme activities and oxidative damage biomarkers were examined to assess the adverse effects of the following 4 commonly detected compounds: perfluoro-octanesulfonate, perfluoro-ocanoic acid, perfluorononanoic acid, and perfluorodecanoic acid, on green mussel (Perna viridis). Quantitative structure-activity relationship (QSAR) models were also established. The results showed that all the tested PFCs are able to induce antioxidant response and oxidative damage on green mussels in a dose-dependent manner. At low exposure levels (0 µg/L-100 µg/L), activation of antioxidant enzymes (catalase [CAT] and superoxide dismutase [SOD]) was observed, which is an adaptive response to the excessive reactive oxygen species induced by PFCs, while at high exposure levels (100 µg/L-10 000 µg/L), PFCs were found to inhibit some enzyme activity (glutathione S-transferase and SOD) where the organism's ability to respond in an adaptive manner was compromised. The oxidative stress under high PFC exposure concentration also led to lipid and DNA damage. PFC-induced oxidative toxicity was found to be correlated with the bioaccumulation potential of PFCs. Based on this relationship, QSAR models were established using the bioaccumulation factor (BAF) as the molecular descriptor for the first time. Compared with previous octanol-water partition coefficient-dependent QSAR models, the BAF-dependent QSAR model is more suitable for the impact assessment of PFCs and thus provides a more accurate description of the toxic behavior of these compounds.

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“…However, the curve for SOD is an inverted "U" shape, which is better modeled by a quadratic function. Non-monotonic curves can be attributed to diverse biological reactions that are initiated in different dose ranges (Gao et al 2009), in this case the ROS promotion and inhibition, binding effect etc. The non-monotonic behavior is worth noting because a measured low response in the biomarker result may not only indicate an insignificant toxic effect, but also severe stress to the organism.…”

Section: Dose-response Curvementioning

confidence: 99%

Bioaccumulation and ecotoxicity study of perfluorinated chemicals

Liu¹

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Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves

Cited by 4 publications

References 36 publications

Model of Hormesis and Its Toxicity Mechanism Based on Quorum Sensing: A Case Study on the Toxicity of Sulfonamides to Photobacterium phosphoreum

Model of Hormesis and Its Toxicity Mechanism Based on Quorum Sensing: A Case Study on the Toxicity of Sulfonamides to Photobacterium phosphoreum

Oxidative toxicity of perfluorinated chemicals in green mussel and bioaccumulation factor dependent quantitative structure–activity relationship

Bioaccumulation and ecotoxicity study of perfluorinated chemicals

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