Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 161, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2022.112849
Keywords
Quercetin; o, p'-DDT; Hepatotoxicity; NADPH oxidase; Nrf2
Categories
Funding
- Shanxi Province Key RESEARCH and Development Plan (Agriculture) Project [201903D221069]
- Natural Sciences Foundation of Shanxi [20210302123462]
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DDT exposure can cause liver cell toxicity, which can be alleviated by quercetin through inhibition of reactive oxygen species production.
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 (delta Psi m), 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.
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