Quercetin protects human liver cells from o,p'-DDT-induced toxicity by suppressing Nrf2 and NADPH oxidase-regulated ROS production.
Food Chem Toxicol
; 161: 112849, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-35122929
ABSTRACT
Epidemiologic studies have revealed that Dichlorodiphenyltrichloroethane (DDT) and its metabolites are associated with liver diseases. However, there has been little emphasis on the mechanism underlying liver toxicity of o,p'-DDT and relevant effective inhibitors investigation. This study indicated o,p'-DDT exposure significantly decreased cell viability and promoted lactate dehydrogenase (LDH) release based on the investigation of cytotoxicity by trypan blue exclusion counts, MTT, and lactate dehydrogenase (LDH) assays. Comet, micronuclei, and DNA-protein crosslinks (DPC) assays demonstrated o,p'-DDT exposure increased the comet parameters, micronuclei frequency, and DPC coefficient. Meanwhile, we found o,p'-DDT induced mitochondria-dependent apoptosis, which is characterized by the loss of mitochondrial membrane potential (Δψm), decreased Bcl-2 expression, and increased protein levels of Bax, cytochrome c, activated-caspase-9, and activated-caspase-3. Furthermore, o,p'-DDT induced reactive oxygen species (ROS) overproduction, decreased the protein levels of nuclear factor erythroid-derived 2-like 2 (Nrf2) in the nuclear, and enhanced the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, quercetin treatment significantly antagonized o,p'-DDT-induced cytotoxicity, genotoxicity, and apoptosis as well as effects on ROS, Nrf2, and NADPH oxidase. Taken together, these findings suggested quercetin could alleviate o,p'-DDT-induced toxicity in HL-7702 cells via inhibiting ROS production, which is modulated by down-regulating nuclear Nrf2 levels and NADPH oxidase expression.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Quercetina
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Especies Reactivas de Oxígeno
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NADPH Oxidasas
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Hepatocitos
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DDT
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Factor 2 Relacionado con NF-E2
Límite:
Humans
Idioma:
En
Revista:
Food Chem Toxicol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China