Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos
This study explored the protective effect and potential mechanism of carvacrol acetate (CAA) on the oxidation of chlorpyrifos (CPF). A model of oxidative stimulus damage was established in Sprague–Dawley rats by subcutaneous injection of the CPF poison. PC12 cells were used to construct an oxidative...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015604 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832590955760320512 |
|---|---|
| author | Hong-Ling Zhou Bei-Bei Wang Xu-Li Fan Xiao-Min Zhang Ying Song |
| author_facet | Hong-Ling Zhou Bei-Bei Wang Xu-Li Fan Xiao-Min Zhang Ying Song |
| author_sort | Hong-Ling Zhou |
| collection | DOAJ |
| description | This study explored the protective effect and potential mechanism of carvacrol acetate (CAA) on the oxidation of chlorpyrifos (CPF). A model of oxidative stimulus damage was established in Sprague–Dawley rats by subcutaneous injection of the CPF poison. PC12 cells were used to construct an oxidative injury model using CPF, and the protective effects and mechanism of action of CAA against CPF-induced oxidative damage were explored in vitro. The key role of Nuclear factor erythroid-2-related factor 2 (Nrf2) in alleviating CPF-induced damage via CAA was further confirmed by administering Nrf2 inhibitors to PC12 cells. Administration of CAA significantly enhanced the locomotor ability of the rats, alleviated neuronal pathological alterations, and increased the number of Nissl bodies, while increasing autophagic bodies. In vitro, CAA promoted cell survival and augmented the mitochondrial membrane potential. It decreased both intra- and extracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), while markedly elevating mitochondrial DNA (mtDNA) copy number. Moreover, PC12 cells treated with Nrf2 inhibitors failed to exhibit any improvement in survival rate when treated with CAA after a toxic insult. Furthermore, ROS and MDA levels were not significantly reduced, SOD enzyme activity did not increase, and mitochondrial membrane potential and mtDNA copy number did not improve. Western blot analysis showed that the expression of Tfam, Beclin1, and LC3II/LC3I proteins in the CAA group decreased significantly after Nrf2 inhibition. These findings suggest that CAA modulates mitochondrial function and autophagy by regulating the Nrf2 signalling pathway to mitigate the toxic damage. Finally, the effect of the autophagy inhibitor, 3-MA, on PC12 cells suggests that CAA promotes mitophagy by participating in the Nrf2 pathway, thereby preventing CPF-induced oxidative stress damage. |
| format | Article |
| id | doaj-art-5c993aa5ad504cefaa6d83f1d4e6022c |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-5c993aa5ad504cefaa6d83f1d4e6022c2025-01-23T05:25:44ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117484Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifosHong-Ling Zhou0Bei-Bei Wang1Xu-Li Fan2Xiao-Min Zhang3Ying Song4Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Jinhua People’s Hospital, Jinhua, Zhejiang 2321000, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; First People’s Hospital of Linping District, Hangzhou, Zhejiang 311103, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Hangzhou King’s Bio-pharmaceutical Technology Co., Ltd., Hangzhou, Zhejiang 310007, China; Correspondence to: Department of Pharmacology, Zhejiang University of Technology, 18 Chao-wang Road, Hangzhou, Zhejiang 310014, PR China.This study explored the protective effect and potential mechanism of carvacrol acetate (CAA) on the oxidation of chlorpyrifos (CPF). A model of oxidative stimulus damage was established in Sprague–Dawley rats by subcutaneous injection of the CPF poison. PC12 cells were used to construct an oxidative injury model using CPF, and the protective effects and mechanism of action of CAA against CPF-induced oxidative damage were explored in vitro. The key role of Nuclear factor erythroid-2-related factor 2 (Nrf2) in alleviating CPF-induced damage via CAA was further confirmed by administering Nrf2 inhibitors to PC12 cells. Administration of CAA significantly enhanced the locomotor ability of the rats, alleviated neuronal pathological alterations, and increased the number of Nissl bodies, while increasing autophagic bodies. In vitro, CAA promoted cell survival and augmented the mitochondrial membrane potential. It decreased both intra- and extracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), while markedly elevating mitochondrial DNA (mtDNA) copy number. Moreover, PC12 cells treated with Nrf2 inhibitors failed to exhibit any improvement in survival rate when treated with CAA after a toxic insult. Furthermore, ROS and MDA levels were not significantly reduced, SOD enzyme activity did not increase, and mitochondrial membrane potential and mtDNA copy number did not improve. Western blot analysis showed that the expression of Tfam, Beclin1, and LC3II/LC3I proteins in the CAA group decreased significantly after Nrf2 inhibition. These findings suggest that CAA modulates mitochondrial function and autophagy by regulating the Nrf2 signalling pathway to mitigate the toxic damage. Finally, the effect of the autophagy inhibitor, 3-MA, on PC12 cells suggests that CAA promotes mitophagy by participating in the Nrf2 pathway, thereby preventing CPF-induced oxidative stress damage.http://www.sciencedirect.com/science/article/pii/S0147651324015604Nrf2ChlorpyrifosCarvacrol acetateOxidative stressMitophagy |
| spellingShingle | Hong-Ling Zhou Bei-Bei Wang Xu-Li Fan Xiao-Min Zhang Ying Song Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos Ecotoxicology and Environmental Safety Nrf2 Chlorpyrifos Carvacrol acetate Oxidative stress Mitophagy |
| title | Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos |
| title_full | Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos |
| title_fullStr | Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos |
| title_full_unstemmed | Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos |
| title_short | Carvacrol acetate activated Nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos |
| title_sort | carvacrol acetate activated nrf2 modulates mitophagy for the treatment of neurocyte oxidative stress induced by chlorpyrifos |
| topic | Nrf2 Chlorpyrifos Carvacrol acetate Oxidative stress Mitophagy |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015604 |
| work_keys_str_mv | AT honglingzhou carvacrolacetateactivatednrf2modulatesmitophagyforthetreatmentofneurocyteoxidativestressinducedbychlorpyrifos AT beibeiwang carvacrolacetateactivatednrf2modulatesmitophagyforthetreatmentofneurocyteoxidativestressinducedbychlorpyrifos AT xulifan carvacrolacetateactivatednrf2modulatesmitophagyforthetreatmentofneurocyteoxidativestressinducedbychlorpyrifos AT xiaominzhang carvacrolacetateactivatednrf2modulatesmitophagyforthetreatmentofneurocyteoxidativestressinducedbychlorpyrifos AT yingsong carvacrolacetateactivatednrf2modulatesmitophagyforthetreatmentofneurocyteoxidativestressinducedbychlorpyrifos |