Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway
Quinocetone (QCT), a member of the quinoxaline 1,4-di-<i>N</i>-oxides (QdNOs) family, can cause genotoxicity and hepatotoxicity, however, the precise molecular mechanisms of QCT are unclear. This present study investigated the protective effect of quercetin on QCT-induced cytotoxicity an...
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MDPI AG
2022-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/8/1498 |
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| author | Chongshan Dai Qinzhi Zhang Linjie Shen Gaurav Sharma Haiyang Jiang Zhanhui Wang Jianzhong Shen |
| author_facet | Chongshan Dai Qinzhi Zhang Linjie Shen Gaurav Sharma Haiyang Jiang Zhanhui Wang Jianzhong Shen |
| author_sort | Chongshan Dai |
| collection | DOAJ |
| description | Quinocetone (QCT), a member of the quinoxaline 1,4-di-<i>N</i>-oxides (QdNOs) family, can cause genotoxicity and hepatotoxicity, however, the precise molecular mechanisms of QCT are unclear. This present study investigated the protective effect of quercetin on QCT-induced cytotoxicity and the underlying molecular mechanisms in human L02 and HepG2 cells. The results showed that quercetin treatment (at 7.5–30 μM) significantly improved QCT-induced cytotoxicity and oxidative damage in human L02 and HepG2 cells. Meanwhile, quercetin treatment at 30 μM significantly inhibited QCT-induced loss of mitochondrial membrane potential, an increase in the expression of the CytC protein and the Bax/Bcl-2 ratio, and an increase in caspases-9 and -3 activity, and finally improved cell apoptosis. Quercetin pretreatment promoted the expression of the phosphorylation of p38, Nrf2, and HO-1 proteins. Pharmacological inhibition of p38 significantly inhibited quercetin-mediated activation of the Nrf2/HO-1 pathway. Consistently, pharmacological inhibitions of the Nrf2 or p38 pathways both promoted QCT-induced cytotoxicity and partly abolished the protective effects of quercetin. In conclusion, for the first time, our results reveal that quercetin could improve QCT-induced cytotoxicity and apoptosis by activating the p38/Nrf2/HO-1 pathway and inhibiting the ROS/mitochondrial apoptotic pathway. Our study highlights that quercetin may be a promising candidate for preventing QdNOs-induced cytotoxicity in humans or animals. |
| first_indexed | 2024-03-09T11:58:53Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T11:58:53Z |
| publishDate | 2022-07-01 |
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| series | Antioxidants |
| spelling | doaj.art-b765e28e103c4d05a9f74a11dc9689af2023-11-30T23:05:58ZengMDPI AGAntioxidants2076-39212022-07-01118149810.3390/antiox11081498Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic PathwayChongshan Dai0Qinzhi Zhang1Linjie Shen2Gaurav Sharma3Haiyang Jiang4Zhanhui Wang5Jianzhong Shen6College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, ChinaAdvanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USACollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, ChinaCollege of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, ChinaQuinocetone (QCT), a member of the quinoxaline 1,4-di-<i>N</i>-oxides (QdNOs) family, can cause genotoxicity and hepatotoxicity, however, the precise molecular mechanisms of QCT are unclear. This present study investigated the protective effect of quercetin on QCT-induced cytotoxicity and the underlying molecular mechanisms in human L02 and HepG2 cells. The results showed that quercetin treatment (at 7.5–30 μM) significantly improved QCT-induced cytotoxicity and oxidative damage in human L02 and HepG2 cells. Meanwhile, quercetin treatment at 30 μM significantly inhibited QCT-induced loss of mitochondrial membrane potential, an increase in the expression of the CytC protein and the Bax/Bcl-2 ratio, and an increase in caspases-9 and -3 activity, and finally improved cell apoptosis. Quercetin pretreatment promoted the expression of the phosphorylation of p38, Nrf2, and HO-1 proteins. Pharmacological inhibition of p38 significantly inhibited quercetin-mediated activation of the Nrf2/HO-1 pathway. Consistently, pharmacological inhibitions of the Nrf2 or p38 pathways both promoted QCT-induced cytotoxicity and partly abolished the protective effects of quercetin. In conclusion, for the first time, our results reveal that quercetin could improve QCT-induced cytotoxicity and apoptosis by activating the p38/Nrf2/HO-1 pathway and inhibiting the ROS/mitochondrial apoptotic pathway. Our study highlights that quercetin may be a promising candidate for preventing QdNOs-induced cytotoxicity in humans or animals.https://www.mdpi.com/2076-3921/11/8/1498quercetinquinocetoneoxidative stressapoptosisp38/Nrf2/HO-1 pathwayNF-κB pathway |
| spellingShingle | Chongshan Dai Qinzhi Zhang Linjie Shen Gaurav Sharma Haiyang Jiang Zhanhui Wang Jianzhong Shen Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway Antioxidants quercetin quinocetone oxidative stress apoptosis p38/Nrf2/HO-1 pathway NF-κB pathway |
| title | Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway |
| title_full | Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway |
| title_fullStr | Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway |
| title_full_unstemmed | Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway |
| title_short | Quercetin Attenuates Quinocetone-Induced Cell Apoptosis In Vitro by Activating the P38/Nrf2/HO-1 Pathway and Inhibiting the ROS/Mitochondrial Apoptotic Pathway |
| title_sort | quercetin attenuates quinocetone induced cell apoptosis in vitro by activating the p38 nrf2 ho 1 pathway and inhibiting the ros mitochondrial apoptotic pathway |
| topic | quercetin quinocetone oxidative stress apoptosis p38/Nrf2/HO-1 pathway NF-κB pathway |
| url | https://www.mdpi.com/2076-3921/11/8/1498 |
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