Joint toxicity of chlorpyrifos and cadmium on the oxidative stress and mitochondrial damage in neuronal cells

Xu, Mingyuan; Wang, Pan; Sun, Ying-Jian; Yang, Lin; Wu, Yi‐Jun

doi:10.1016/j.fct.2017.03.013

Cited by 52 publications

(38 citation statements)

References 32 publications

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“…In the present study, we aimed to use metabolomics analysis to study the individual and combined subchronic toxicity of low dose of CPF and Cd on the liver. The low doses of CPF and Cd used in our study (1.7, 0.7 mg/kg/d, respectively) are close to the level of possible human exposure to CPF and Cd in the working environment as well as from consumption of contaminated food (Xu et al, 2017). Our results indicated that CPF, Cd and their mixtures could induce the hepatotoxicity, and they disrupted the liver metabolism.…”

Section: Introductionsupporting

confidence: 47%

“…Cd can be enriched in the food chain and accumulated in human body for a long time with half-life of [20][21][22][23][24][25][26][27][28][29][30] years (Järup et al, 1983), and does serious harm to several organs. Chronic Cd exposure induced renal dysfunction, hepatotoxicity and osteoporosis in experimental animals model (Brzoska et al, 2005;Renugadevi and Prabu, 2010;Siddiqui, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

Wang

Sun

et al. 2017

Toxicology

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Section: Introductionsupporting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

Wang

Sun

et al. 2017

Toxicology

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“…As far as we know, no serum biomarkers are available to diagnose the toxicosis of CPF, Cd, and CPF plus Cd at their low doses. The observation of body weight and relative organ weight in all treatment groups suggests that CPF and Cd cause unobvious poisoning in the treated groups, except at high dose of CPF 15,16 . For the blood biochemical analysis, overall, no obvious change was observed in the low-dose individual CPF-or Cd-treated groups although high-dose Cd induced the increase of the tested parameters and the middle dose of Cd, CPF, or Cd plus CPF caused changes of only some of the parameters.…”

Section: Discussionmentioning

confidence: 85%

“…As the technology advances, new methodologies such as omics approaches are developed, and great progress has been made in the study of mixture toxicology, which increases our ability to predict the potential risks of exposure to mixtures 12 .The acute toxicity of CPF and Cd are well understood 13,14 . We have reported that chronic exposure to CPF and Cd individually and in combination caused neurotoxicity and hepatotoxicity 15,16 . We found that CPF and Cd disturbed energy and amino acids metabolism in the brain and liver.…”

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confidence: 99%

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Identification of metabolite biomarkers in serum of rats exposed to chlorpyrifos and cadmium

Wang

Sun

et al. 2020

Sci Rep

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Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometerbased metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.Chlorpyrifos (CPF) is a widely used organophosphorus insecticide with cholinergic toxicity 1,2 . CPF exposure can induce severe toxicity in multiple organs 3 . Cadmium (Cd) is a persistent toxic metal with very long half-life 4 . Chronic Cd exposure induces toxicity in kidneys, liver, and bones 5-8 . Due to their toxicity to different target organs, CPF and Cd pose significant threats to public health.CPF and Cd are widespread environmental toxicants which often coexist in water, air, and soil 3,9 . Given that environmental toxicants are widespread, organisms are seldom exposed to only one chemical. Thus, it is important to study the combined toxicity of multiple toxicants. More and more studies suggest that combined exposure to different chemicals can potentiate the toxicity of single chemical alone 2,10,11 . As the technology advances, new methodologies such as omics approaches are developed, and great progress has been made in the study of mixture toxicology, which increases our ability to predict the potential risks of exposure to mixtures 12 .The acute toxicity of CPF and Cd are well understood 13,14 . We have reported that chronic exposure to CPF and Cd individually and in combination caused neurotoxicity and hepatotoxicity 15,16 . We found that CPF and Cd disturbed energy and amino acids metabolism in the brain and liver. Therefore, in this study, we try to identify the biomarkers in serum, upon exposure to CPF, Cd, and their mixture.Metabolomics is a very useful approach for toxicological studies because it can characterize the changes of metabolite levels induced by toxic chemicals and identify the specific biomarkers for each toxicant 17,18 . In the present study, we aim to use metabolomics analysis in se...

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Cadmium‐induced global DNA hypermethylation promoting mitochondrial dynamics dysregulation in hippocampal neurons

Geng,

An,

Song

et al. 2023

Environmental Toxicology

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Environmental cadmium exposure during pregnancy or adolescence can cause neurodevelopmental toxicity, lead to neurological impairment, and reduce cognitive abilities, such as learning and memory. However, the mechanisms by which cadmium causes neurodevelopmental toxicity and cognitive impairment are still not fully elucidated. This study used hippocampal neurons cultured in vitro to observe the impact of cadmium exposure on mitochondrial dynamics and apoptosis. Exposure to 5 μM cadmium causes degradation of hippocampal neuron cell bodies and axons, morphological destruction, low cell viability, and apoptosis increase. Cadmium exposure upregulates the expression of mitochondrial fission proteins Drp1 and Fis1, reduces the expression of mitochondrial fusion‐related proteins MFN1, MFN2, and OPA1, as well as reduces the expression of PGC‐1a. Mitochondrial morphology detection demonstrated that cadmium exposure changes the morphological structure of mitochondria in hippocampal neurons, increasing the number of punctate and granular mitochondria, reducing the number of tubular and reticular mitochondria, decreasing mitochondrial mass, dissipating mitochondrial membrane potential (ΔΨm), and reducing adenosine triphosphate (ATP) production. Cadmium exposure increases the global methylation level of the genome and upregulates the expression of DNMT1 and DNMT3α in hippocampal neurons. 5‐Aza‐CdR reduces cadmium‐induced genome methylation levels in hippocampal neurons, increases the number of tubular and reticular mitochondria, and promotes cell viability. In conclusion, cadmium regulates the expression of mitochondrial dynamics‐related proteins by increasing hippocampal neuron genome methylation, changing mitochondrial morphology and function, and exerting neurotoxic effects.

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Joint toxicity of chlorpyrifos and cadmium on the oxidative stress and mitochondrial damage in neuronal cells

Cited by 52 publications

References 32 publications

Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

Identification of metabolite biomarkers in serum of rats exposed to chlorpyrifos and cadmium

Cadmium‐induced global DNA hypermethylation promoting mitochondrial dynamics dysregulation in hippocampal neurons

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