Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network

Yang, Lihua; Zhou, Bingsheng; Zha, Jinmiao; Wang, Zijian

doi:10.1016/j.chemosphere.2016.07.034

Cited by 9 publications

(2 citation statements)

References 52 publications

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“…CLD is considered as an endocrine disruptor notably by interacting with the estrogen receptor α (ERα) (Hammond et al 1979;Yang et al 2016). Even if the targets of CLD are not fully identified, this mechanism could explain in part its carcinogenicity and its developmental toxicity (Multigner et al 2010;Clere et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound

Legeay

Billat

Clere

et al. 2017

Environ Sci Pollut Res

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Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules. Mutagenicity and genotoxicity were investigated using the Ames's technique on Salmonella typhimurium and the in vitro micronucleus micromethod with TK6 human lymphoblastoid cells. The proangiogenic properties were evaluated on the in vitro capillary network formation of human primary endothelial cells. Like CLD, the dechlorinated derivatives of CLD studied were devoid of genotoxic and mutagenic activity. In the assay targeting angiogenic properties, significantly lower microvessel lengths formed by endothelial cells were observed for the CLD-3Cl-treated cells compared to the CLD-treated cells for two of the three tested concentrations. These results suggest that dechlorinated CLD derivatives are devoid of mutagenicity and genotoxicity and have lower proangiogenic properties than CLD.

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Section: Introductionmentioning

confidence: 99%

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound

Legeay

Billat

Clere

et al. 2017

Environ Sci Pollut Res

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“…Chlordecone has been shown to bioaccumulate and interrupt the molting process by decreasing the concentration of 20-hydroxyecdysone and the chitobiase activity in Macrobrachium rosenbergii (Lafontaine et al, 2016). Chlordecone has also shown to cause endocrine disruption by showing similarities to estrogen receptors and cytochrome P450 where it increased vitellogenin in females, degenerated gonads and increased the concentrations of plasma estradiol in both male and female rare minnow (Yang et al, 2016). Fish are the final chain in an aquatic food web and an important food source for humans, so the exposure of chlordecone can be transferred into humans through the food chain.…”

Section: Introductionmentioning

confidence: 99%

Evidence for Chlordecone-Stimulated Oxidative Stress in Different Tissues of the Cichlid Fish, Pseudetroplus Maculatus (Bloch, 1795)

Asifa

Chitra

2017

Croatian Journal of Fisheries

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The present study was designed to assess the effect of chlordecone on the stimulation of oxidative stress in gill, liver and brain tissues of the cichlid fish, Pseudetroplus maculatus. Fishes were exposed to chlordecone at two sublethal concentrations, 3.5 and 7 μg/L, for 24, 72 and 96 h, maintaining ten animals in each group. Chlordecone treatment did not alter the body weight of the animal. However, significant increase in the secretion of mucous and decrease in the weights of gill, brain and hepatosomatic index were observed at 7 μg/L of chlordecone treatment only after 96 h. Gill tissue showed significant increase in the activities of superoxide dismutase, catalase and glutathione reductase along with elevated levels of hydrogen peroxide and lipid peroxidation in concentration and timedependent manner. This could be the defensive mechanism of gill tissue to escape the toxic effects of chlordecone. In the liver tissue, superoxide dismutase activity was increased by 39% at 3.5 μg/L and by 73% at 7 μg/L of chlordecone treatment. Activities of catalase and glutathione reductase were decreased 3 to 9 times at 3.5 and 7 μg/L concentrations, respectively, with concomitant increase in hydrogen peroxide generation (17 to 28 times) and lipid peroxidation (3 to 7 times) at the end of 96 h, which reveals the failure of hepatic antioxidant system to prevent free radical generation owing to chlordecone exposure. Activities of all antioxidant enzymes in the brain were inhibited by 29 to 80% along with the induction of hydrogen peroxide (13 to 20 times) and lipid peroxidation (6 to 11 times), thereby indicating imbalance in the antioxidant status. Activities of gill and liver marker enzyme - alkaline phosphatase - and acetylcholinesterase in brain were decreased. Therefore, imbalance in the antioxidant defence system as a result of chlordecone toxicity could lead to susceptible oxidative stress in various tissues of the fish.

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Environmental Factors

Leisegang¹,

Henkel²

2020

Male Infertility

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Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network

Cited by 9 publications

References 52 publications

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound

Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound

Evidence for Chlordecone-Stimulated Oxidative Stress in Different Tissues of the Cichlid Fish, Pseudetroplus Maculatus (Bloch, 1795)

Environmental Factors

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