{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:32:37Z","timestamp":1793644357073,"version":"4.5.1"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFD0501208"],"award-info":[{"award-number":["2016YFD0501208"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["32172921"],"award-info":[{"award-number":["32172921"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["KYCX22-3548"],"award-info":[{"award-number":["KYCX22-3548"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2016YFD0501208"],"award-info":[{"award-number":["2016YFD0501208"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172921"],"award-info":[{"award-number":["32172921"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["KYCX22-3548"],"award-info":[{"award-number":["KYCX22-3548"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ordinary University Graduate Student Scientific Research Innovation Projects in Jiangsu Province","award":["2016YFD0501208"],"award-info":[{"award-number":["2016YFD0501208"]}]},{"name":"Ordinary University Graduate Student Scientific Research Innovation Projects in Jiangsu Province","award":["32172921"],"award-info":[{"award-number":["32172921"]}]},{"name":"Ordinary University Graduate Student Scientific Research Innovation Projects in Jiangsu Province","award":["KYCX22-3548"],"award-info":[{"award-number":["KYCX22-3548"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Zearalenone (ZEA) is a common mycotoxin that induces oxidative stress (OS) and affects the male reproductive system in animals. Resveratrol (RSV) has good antioxidant activity and can activate nuclear factor erythroid 2-related factor (Nrf2) to protect cells through the phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (Akt) signaling pathway. The objective of this study was to investigate the protective effect and the mechanism of RSV on OS and apoptosis in TM4 cells induced by ZEA. Prior to being exposed to ZEA, TM4 cells were pretreated with RSV or the PI3K\/Akt inhibitor LY294002. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assays. Flow cytometry was used to determine the level of apoptosis and intracellular reactive oxygen species (ROS). The expression of poly ADP-ribose polymerase (PARP), caspase-3, BCL2-associated X (Bax)\/B-cell lymphoma-2 (Bcl-2), and PI3K\/Akt-mediated Nrf2\/heme oxygenase 1 (HO-1) signaling pathway-related proteins was evaluated by Western blotting. Nrf2 siRNA transfection and LY294002 treatment were used to investigate the role of the Nrf2\/HO-1 and PI3K\/Akt signaling pathways in RSV alleviation of ZEA-induced OS. The results showed that pretreatment with RSV significantly reduced the expression of apoptosis-related proteins and increased cell viability. Catalase (CAT) activity and glutathione (GSH) levels were also increased, whereas malondialdehyde (MDA) and ROS levels decreased (p &lt; 0.05). RSV also upregulated Akt phosphorylation, Nrf2 nuclear translocation, and HO-1 expression under conditions of OS (p &lt; 0.05). Transfection with Nrf2 siRNA abolished the protective effects of RSV against ZEA-induced cytotoxicity (p &lt; 0.05), ROS accumulation (p &lt; 0.05), and apoptosis (p &lt; 0.05). LY294002 completely blocked the RSV-mediated increase in Nrf2 nuclear translocation (p &lt; 0.05), HO-1 expression (p &lt; 0.05), and cytoprotective activity (p &lt; 0.05). Collectively, the above findings indicate that RSV can protect against ZEA-induced OS and apoptosis in TM4 cells by PI3K\/Akt-mediated activation of the Nrf2\/HO-1 signaling pathway.<\/jats:p>","DOI":"10.3390\/toxins14110733","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T11:53:51Z","timestamp":1666785231000},"page":"733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Role of PI3K\/Akt-Mediated Nrf2\/HO-1 Signaling Pathway in Resveratrol Alleviation of Zearalenone-Induced Oxidative Stress and Apoptosis in TM4 Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Wenlin","family":"Xu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youtian","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayi","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9071-8363","authenticated-orcid":false,"given":"Zongping","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-0751","authenticated-orcid":false,"given":"Jianchun","family":"Bian","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, China"},{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China"},{"name":"Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1080\/10408398.2019.1655388","article-title":"Occurrence and toxicity of a fusarium mycotoxin, zearalenone","volume":"60","author":"Rai","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"112737","DOI":"10.1016\/j.ecoenv.2021.112737","article-title":"Lycopene attenuates zearalenone-induced oxidative damage of piglet sertoli cells through the nuclear factor erythroid-2 related factor 2 signaling pathway","volume":"225","author":"Cao","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141872","DOI":"10.1016\/j.scitotenv.2020.141872","article-title":"Biochemical and molecular responses of maize (Zea mays L.) to 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH) diastereomers: Oxidative stress, DNA damage, antioxidant enzyme gene expression and diversity of root exudates","volume":"753","author":"Huang","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/ps.6055","article-title":"Isochamaejasmin induces toxic effects on Helicoverpa zea via DNA damage and mitochondria-associated apoptosis","volume":"77","author":"Ren","year":"2021","journal-title":"Pest Manag. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2020.01.010","article-title":"ZEA-induced autophagy in TM4 cells was mediated by the release of Ca2+ activates CaMKK\u03b2-AMPK signaling pathway in the endoplasmic reticulum","volume":"323","author":"Feng","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Wang, H., Wang, J., Han, S., Zhang, Y., Ma, M., Zhu, Q., Zhang, K., and Yin, H. (2021). Zearalenone Induces Apoptosis and Cytoprotective Autophagy in Chicken Granulosa Cells by PI3K-AKT-mTOR and MAPK Signaling Pathways. Toxins, 13.","DOI":"10.3390\/toxins13030199"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40104-021-00661-4","article-title":"Invited review: Remediation strategies for mycotoxin control in feed","volume":"13","author":"Liu","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41419-019-1782-z","article-title":"Multiple signaling pathways in Sertoli cells: Recent findings in spermatogenesis","volume":"10","author":"Ni","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e06868","DOI":"10.1016\/j.heliyon.2021.e06868","article-title":"Pentoxifylline improves the survival of spermatogenic cells via oxidative stress suppression and upregulation of PI3K\/AKT pathway in mouse model of testicular torsion-detorsion","volume":"7","author":"Dhulqarnain","year":"2021","journal-title":"Heliyon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.neuroscience.2009.02.086","article-title":"Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation","volume":"161","author":"Barhwal","year":"2009","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1002\/jcp.29219","article-title":"Nrf2-ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms","volume":"235","author":"Shaw","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.bbrc.2010.04.117","article-title":"Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K\/Akt pathway","volume":"396","author":"Chartoumpekis","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1007\/s12011-020-02398-z","article-title":"Epigallocatechin-3-gallate Alleviates Vanadium-Induced Reduction of Antioxidant Capacity via Keap1-Nrf2-sMaf Pathway in the Liver, Kidney, and Ovary of Laying Hens","volume":"199","author":"Ma","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110234","DOI":"10.1016\/j.biopha.2020.110234","article-title":"The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway","volume":"127","author":"Farkhondeh","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1002\/ptr.6168","article-title":"Protective effects of Vitis vinifera (grapes) and one of its biologically active constituents, resveratrol, against natural and chemical toxicities: A comprehensive review","volume":"32","author":"Tabeshpour","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mirzaei, S., Zarrabi, A., Hashemi, F., Zabolian, A., Saleki, H., Azami, N., Hamzehlou, S., Farahani, M.V., Hushmandi, K., and Ashrafizadeh, M. (2021). Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery. Antioxidants, 10.","DOI":"10.3390\/antiox10030349"},{"key":"ref_17","first-page":"13","article-title":"Health benefits of resveratrol administration","volume":"66","author":"Galiniak","year":"2019","journal-title":"Acta Biochim. Pol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.bbr.2016.02.030","article-title":"Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats","volume":"305","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lin, M.C., Liu, C.C., Lin, Y.C., and Liao, C.S. (2021). Resveratrol Protects against Cerebral Ischemic Injury via Restraining Lipid Peroxidation, Transition Elements, and Toxic Metal Levels, but Enhancing Anti-Oxidant Activity. Antioxidants, 10.","DOI":"10.3390\/antiox10101515"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104800","DOI":"10.1016\/j.micpath.2021.104800","article-title":"Resveratrol impacts in oxidative stress in liver during Trypanosoma cruzi infection","volume":"153","author":"Fracasso","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101271","DOI":"10.1016\/j.arr.2021.101271","article-title":"The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer\u2019s disease pathology: From antioxidant to epigenetic therapy","volume":"67","author":"Izquierdo","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/biof.1399","article-title":"Role of resveratrol in regulation of cellular defense systems against oxidative stress","volume":"44","author":"Truong","year":"2018","journal-title":"Biofactors"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7591840","DOI":"10.1155\/2019\/7591840","article-title":"Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K\/Akt-Mediated Nrf2 Signaling Pathway","volume":"2019","author":"Zhuang","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.3233\/JAD-191032","article-title":"GABAB Receptor-Mediated PI3K\/Akt Signaling Pathway Alleviates Oxidative Stress and Neuronal Cell Injury in a Rat Model of Alzheimer\u2019s Disease","volume":"76","author":"Sun","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10565-019-09467-7","article-title":"Relevance of Erk1\/2-PI3K\/Akt signaling pathway in CEES-induced oxidative stress regulates inflammation and apoptosis in keratinocytes","volume":"35","author":"Sabnam","year":"2019","journal-title":"Cell Biol. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26724","DOI":"10.1007\/s11356-017-0123-y","article-title":"Protective effect of proanthocyanidin on mice Sertoli cell apoptosis induced by zearalenone via the Nrf2\/ARE signalling pathway","volume":"24","author":"Long","year":"2017","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1007\/s11356-016-7886-4","article-title":"Proanthocyanidin protects against acute zearalenone-induced testicular oxidative damage in male mice","volume":"24","author":"Long","year":"2017","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zada, S., Alam, S., Ayoubi, S.A., Shakeela, Q., Nisa, S., Niaz, Z., Khan, I., Ahmed, W., Bibi, Y., and Ahmed, S. (2021). Biological Transformation of Zearalenone by Some Bacterial Isolates Associated wit Ruminant and Food Samples. Toxins, 13.","DOI":"10.3390\/toxins13100712"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.fct.2018.06.003","article-title":"Toxic effects of zearalenone on gametogenesis and embryonic development: A molecular point of review","volume":"119","author":"Yang","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ropejko, K., and Twaru\u017cek, M. (2021). Zearalenone and Its Metabolites-General Overview, Occurrence, and Toxicity. Toxins, 13.","DOI":"10.3390\/toxins13010035"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Azam, M.S., Yu, D., Liu, N., and Wu, A. (2019). Degrading Ochratoxin A and Zearalenone Mycotoxins Using a Multifunctional Recombinant Enzyme. Toxins, 11.","DOI":"10.3390\/toxins11050301"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1080\/01913123.2022.2067929","article-title":"Histomorphological changes and molecular mechanisms underlying the ameliorative effect of resveratrol on the liver of silver nanoparticles-exposed rats","volume":"46","author":"Abdelrahman","year":"2022","journal-title":"Ultrastruct. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Qin, X., Cao, M., Lai, F., Yang, F., Ge, W., Zhang, X., Cheng, S., Sun, X., Qin, G., and Shen, W. (2015). Oxidative stress induced by zearalenone in porcine granulosa cells and its rescue by curcumin in vitro. PLoS ONE., 10.","DOI":"10.1371\/journal.pone.0127551"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111405","DOI":"10.1016\/j.fct.2020.111405","article-title":"Proteomic analysis using iTRAQ technology reveals the toxic effects of zearalenone on the leydig cells of rats","volume":"141","author":"Wang","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"60276","DOI":"10.1007\/s11356-021-14052-9","article-title":"N-acetylcysteine ameliorate cytotoxic injury in piglets sertoli cells induced by zearalenone and deoxynivalenol","volume":"28","author":"Cao","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gruber-Dorninger, C., Jenkins, T., and Schatzmayr, G. (2019). Global Mycotoxin Occurrence in Feed: A Ten-Year Survey. Toxins, 11.","DOI":"10.3390\/toxins11070375"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40104-021-00603-0","article-title":"Occurrence of Aflatoxin B1, deoxynivalenol and zearalenone in feeds in China during 2018-2020","volume":"12","author":"Zhao","year":"2021","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mahato, D.K., Devi, S., Pandhi, S., Sharma, B., Maurya, K.K., Mishra, S., Dhawan, K., Selvakumar, R., Kamle, M., and Mishra, A.K. (2021). Occurrence, Impact on Agriculture, Human Health, and Management Strategies of Zearalenone in Food and Feed: A Review. Toxins, 13.","DOI":"10.3390\/toxins13020092"},{"key":"ref_39","first-page":"1934578X1801300923","article-title":"A Systematic Review on Natural Antioxidant Properties of Resveratrol","volume":"13","author":"Colica","year":"2018","journal-title":"Nat. Prod. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1080\/14764172.2018.1469767","article-title":"Resveratrol as an active ingredient for cosmetic and dermatological applications: A review","volume":"21","author":"Arct","year":"2019","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_41","first-page":"101139","article-title":"Study the antioxidant effects of blue-green algae Spirulina extract on ROS and MDA production in human lung cancer cells","volume":"28","author":"Tajvidi","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kuthati, Y., Busa, P., Tummala, S., Rao, V.N., Davuluri, V.N.G., Ho, Y.P., and Wong, C.S. (2021). Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System. Antioxidants, 10.","DOI":"10.3390\/antiox10020195"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111840","DOI":"10.1016\/j.fct.2020.111840","article-title":"Protective effect of resveratrol against toxicity induced by the mycotoxin, zearalenone in a rat model","volume":"146","author":"Virk","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"126654","DOI":"10.1016\/j.chemosphere.2020.126654","article-title":"Identification of heme oxygenase-1 from golden pompano (Trachinotus ovatus) and response of Nrf2\/HO-1 signaling pathway to copper-induced oxidative stress","volume":"253","author":"Xie","year":"2020","journal-title":"Chemosphere"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00011-019-01311-2","article-title":"Anti-inflammatory activity of the extracts from Rodgersia podophylla leaves through activation of Nrf2\/HO-1 pathway, and inhibition of NF-\u03baB and MAPKs pathway in mouse macrophage cells","volume":"69","author":"Kim","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.toxicon.2022.03.011","article-title":"Zingerone attenuates zearalenone-induced steroidogenesis impairment and apoptosis in TM3 Leydig cell line","volume":"211","author":"Shahidi","year":"2022","journal-title":"Toxicon"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109851","DOI":"10.1016\/j.biopha.2020.109851","article-title":"Hydrazinocurcumin and 5-fluorouracil enhance apoptosis and restrain tumorigenicity of HepG2 cells via disrupting the PTEN-mediated PI3K\/Akt signaling pathway","volume":"129","author":"Zhou","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3727\/096504009787721195","article-title":"Suppression of prometastatic phenotype of highly metastatic androgen-independent rat prostate cancer MLL cell line by PI3K inhibitor LY294002","volume":"17","author":"Prawettongsopon","year":"2009","journal-title":"Oncol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"829830","DOI":"10.3389\/fphar.2022.829830","article-title":"Metformin Promotes Differentiation and Attenuates H2O2-Induced Oxidative Damage of Osteoblasts via the PI3K\/AKT\/Nrf2\/HO-1 Pathway","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12013-022-01064-6","article-title":"The Protective Role of Celastrol in Renal Ischemia-Reperfusion Injury by Activating Nrf2\/HO-1, PI3K\/AKT Signaling Pathways, Modulating NF-\u03bab Signaling Pathways, and Inhibiting ERK Phosphorylation","volume":"80","author":"Younis","year":"2022","journal-title":"Cell Biochem. Biophys."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/11\/733\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:03:00Z","timestamp":1760144580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/11\/733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,26]]},"references-count":50,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["toxins14110733"],"URL":"https:\/\/doi.org\/10.3390\/toxins14110733","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,26]]}}}