Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury
This study investigates the protective effect of baicalein on carbon tetrachloride (CCl<sub>4</sub>)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10...
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/6/976 |
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| author | Chongshan Dai Hui Li Yang Wang Shusheng Tang Tony Velkov Jianzhong Shen |
| author_facet | Chongshan Dai Hui Li Yang Wang Shusheng Tang Tony Velkov Jianzhong Shen |
| author_sort | Chongshan Dai |
| collection | DOAJ |
| description | This study investigates the protective effect of baicalein on carbon tetrachloride (CCl<sub>4</sub>)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl<sub>4</sub> injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl<sub>4</sub> exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl<sub>4</sub>-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl<sub>4</sub>. In vitro, baicalein treatment improved CCl<sub>4</sub> -induced decreases of cell viabilities and knockdown of <i>Nrf2</i> and arachidonate 12-lipoxygenase (<i>ALOX12</i>) genes partly abolished the protective effect of baicalein on CCl<sub>4</sub> -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl<sub>4</sub>-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways. |
| first_indexed | 2024-03-10T10:17:40Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:17:40Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-81b94e2388f44293b88c28e49419002b2023-11-22T00:42:18ZengMDPI AGAntioxidants2076-39212021-06-0110697610.3390/antiox10060976Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver InjuryChongshan Dai0Hui Li1Yang Wang2Shusheng Tang3Tony Velkov4Jianzhong Shen5College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, ChinaBeijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, 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, ChinaDepartment of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, AustraliaCollege of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, ChinaThis study investigates the protective effect of baicalein on carbon tetrachloride (CCl<sub>4</sub>)-induced acute liver injury and the underlying molecular mechanisms. Mice were orally administrated baicalein at 25 and 100 mg/kg/day for 7 consecutive days or ferrostatin-1 (Fer-1) at 10 mg/kg was i.p. injected in mice at 2 and 24 h prior to CCl<sub>4</sub> injection or the vehicle. Our results showed that baicalein or Fer-1 supplementation significantly attenuated CCl<sub>4</sub> exposure-induced elevations of serum alanine aminotransferase and aspartate aminotransferase, and malondialdehyde levels in the liver tissues and unregulated glutathione levels. Baicalein treatment inhibited the nuclear factor kappa-B (NF-κB) pathway, activated the erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in liver tissues, and markedly improved CCl<sub>4</sub>-induced apoptosis, inflammation and ferroptosis in liver tissues exposed with CCl<sub>4</sub>. In vitro, baicalein treatment improved CCl<sub>4</sub> -induced decreases of cell viabilities and knockdown of <i>Nrf2</i> and arachidonate 12-lipoxygenase (<i>ALOX12</i>) genes partly abolished the protective effect of baicalein on CCl<sub>4</sub> -induced cytotoxicity in HepG2 cells. In conclusion, our results reveal that baicalein supplementation ameliorates CCl<sub>4</sub>-induced acute liver injury in mice by upregulating the antioxidant defense pathways and downregulating oxidative stress, apoptosis, inflammation and ferroptosis, which involved the activation of Nrf2 pathway and the inhibition of ALOX12 and NF-κB pathways.https://www.mdpi.com/2076-3921/10/6/976baicaleinoxidative stressferroptosisacute liver injuryALOX12 pathwayNrf2 pathway |
| spellingShingle | Chongshan Dai Hui Li Yang Wang Shusheng Tang Tony Velkov Jianzhong Shen Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury Antioxidants baicalein oxidative stress ferroptosis acute liver injury ALOX12 pathway Nrf2 pathway |
| title | Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury |
| title_full | Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury |
| title_fullStr | Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury |
| title_full_unstemmed | Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury |
| title_short | Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury |
| title_sort | inhibition of oxidative stress and alox12 and nf κb pathways contribute to the protective effect of baicalein on carbon tetrachloride induced acute liver injury |
| topic | baicalein oxidative stress ferroptosis acute liver injury ALOX12 pathway Nrf2 pathway |
| url | https://www.mdpi.com/2076-3921/10/6/976 |
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