Glycyrrhizin alleviates varicellovirus bovinealpha 1-induced oxidative stress, inflammation, and apoptosis in MDBK cells by inhibiting NF-κB/NLRP3 axis through the Nrf2 signalling pathway.
Apoptosis
Glycyrrhizin
Inflammation
Oxidative stress
Varicellovirus Bovinealpha 1
Journal
Veterinary research communications
ISSN: 1573-7446
Titre abrégé: Vet Res Commun
Pays: Switzerland
ID NLM: 8100520
Informations de publication
Date de publication:
27 Oct 2023
27 Oct 2023
Historique:
received:
10
06
2023
accepted:
11
10
2023
medline:
27
10
2023
pubmed:
27
10
2023
entrez:
27
10
2023
Statut:
aheadofprint
Résumé
Varicellovirus bovinealpha 1 (BoAHV-1) is one of the crucial pathogens of bovine respiratory diseases, and its pathogenic mechanism involves oxidative stress, inflammation response, and apoptosis. Glycyrrhizin (GLY) possesses powerful antiviral, antioxidant, anti-inflammatory, and anti-apoptotic bioactivities. However, the anti-BoAHV-1 activity of GLY and its role in BoAHV-1-induced oxidative stress, inflammation, and apoptosis remain unclear. Therefore, the current study investigated the anti-BoAHV-1 effect of GLY and its ability to alleviate BoAHV-1-induced oxidative stress, inflammation, and apoptosis using an in vitro model (MDBK cells). Our results showed that BoAHV-1 titers significantly increased in MDBK cells after infection, and GLY reduced the BoAHV-1 titers in MDBK cells exposed to it. Furthermore, Interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, phosphorylated NF-κB p65 (p-NF-κB p65), the NLR pyrin domain containing 3 (NLRP3), Caspase-1, and Cleaved Caspase-3 levels were significantly upregulated when MDBK cells were challenged with BoAHV-1. In BAY 11-7085 (a specific NF-κB inhibitor) treated MDBK cells, IL-1β, IL-8, TNF-α, p-NF-κB p65, NLRP3, Caspase-1, and Cleaved Caspase-3 levels were downregulated. Notably, GLY treatment had the same trend as the BAY 11-7085 treatment. Thus, these results suggested that GLY exerted anti-inflammatory and anti-apoptotic activities by blocking NF-κB/NLRP3 axis. In addition, after BoAHV-1 infection, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and p-NF-κB p65 and apoptosis rate were increased, and catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities, as well as NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression were repressed. Compared with BoAHV-1-infected MDBK cells, GLY treatment significantly downregulated intracellular ROS, MDA, and p-NF-κB p65 levels and apoptotic rates and significantly increased intracellular CAT and GSH-Px enzyme activities and Nrf2 expression. Additionally, ML385 (a specific Nrf2 inhibitor) abolished the enhancing effect of GLY on Nrf2 and the attenuating effect on ROS, p-NF-κB p65, and apoptosis. These results suggested that GLY had an anti-BoAHV-1 effect and could mitigate BoAHV-1-induced oxidative stress, inflammation, and apoptosis by activating the Nrf2 signalling and restraining NF-κB/NLRP3 axis.
Identifiants
pubmed: 37889426
doi: 10.1007/s11259-023-10242-7
pii: 10.1007/s11259-023-10242-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Afroz S, Garg R, van Fodje M (2018) The Major Tegument Protein of Bovine Herpesvirus 1, VP8, Interacts with DNA Damage Response Proteins and Induces Apoptosis. J Virol 92(15). https://doi.org/10.1128/jvi.00773-18 . Drunen Littel-van den Hurk
Bao L, Li J, Zha D, Zhang L, Gao P, Yao T, Wu X (2018) Chlorogenic acid prevents diabetic Nephropathy by inhibiting oxidative stress and inflammation through modulation of the Nrf2/HO-1 and NF-ĸB pathways. Int Immunopharmacol 54:245–253. https://doi.org/10.1016/j.intimp.2017.11.021
doi: 10.1016/j.intimp.2017.11.021
pubmed: 29161661
Bao XD, Zu YY, Wang BX, Li MY, Jiang FS, Qian CD, Zhou FM, Ding ZS (2023) Coelonin protects against PM(2) (.5) -induced macrophage damage via suppressing TLR4/NF-κB/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro. Environ Toxicol 38(5):1196–1210. https://doi.org/10.1002/tox.23772
doi: 10.1002/tox.23772
pubmed: 36880448
Bielefeldt Ohmann H, Babiuk LA, Harland R (1991) Cytokine synergy with viral cytopathic effects and bacterial products during the pathogenesis of respiratory tract Infection. Clin Immunol Immunopathol 60(2):153–170. https://doi.org/10.1016/0090-1229(91)90060-n
doi: 10.1016/0090-1229(91)90060-n
pubmed: 1649026
Boakye YD, Osafo N, Oppong-Kyekyeku J, Abotsi WKM, Boakye-Gyasi E, Heiss E, Agyare C (2022) Regulation of Nrf2 and NF-κB activities may contribute to the anti-inflammatory mechanism of xylopic acid. Inflammopharmacology 30(5):1835–1841. https://doi.org/10.1007/s10787-022-00950-y
doi: 10.1007/s10787-022-00950-y
pubmed: 35260973
Chang L, Zhu L (2020) Dewormer drug fenbendazole has antiviral effects on BoHV-1 productive Infection in cell cultures. J Vet Sci 21(5):e72. https://doi.org/10.4142/jvs.2020.21.e72
doi: 10.4142/jvs.2020.21.e72
pubmed: 33016019
pmcid: 7533386
Dai H, Wu J, Yang H, Guo Y, Di H, Gao M, Wang J (2022) Construction of BHV-1 UL41 defective virus using the CRISPR/Cas9 system and analysis of viral replication Properties. Front Cell Infect Microbiol 12:942987. https://doi.org/10.3389/fcimb.2022.942987
doi: 10.3389/fcimb.2022.942987
pubmed: 35873151
pmcid: 9304932
Devireddy LR, Jones CJ (1999) Activation of caspases and p53 by bovine herpesvirus 1 Infection results in programmed cell death and efficient virus release. J Virol 73(5):3778–3788. https://doi.org/10.1128/jvi.73.5.3778-3788.1999
doi: 10.1128/jvi.73.5.3778-3788.1999
pubmed: 10196272
pmcid: 104155
Duan E, Zhang B, Liang X, Jing H, Liu C, Zhang F, Huang J, Su L, Wang J (2021) Effects of glycyrrhizin on the growth cycle and ATPase activity of PRRSV-2-infected MARC-145 cells. Res Vet Sci 138:30–38. https://doi.org/10.1016/j.rvsc.2021.05.011
doi: 10.1016/j.rvsc.2021.05.011
pubmed: 34091227
Durgut R, Ataseven VS, Sağkan-Öztürk A, Oztürk OH (2013) Evaluation of total oxidative stress and total antioxidant status in cows with natural bovine herpesvirus-1 Infection. J Anim Sci 91(7):3408–3412. https://doi.org/10.2527/jas.2012-5516
doi: 10.2527/jas.2012-5516
pubmed: 23798525
Ercan I, Cilaker Micili S, Soy S, Engur D, Tufekci KU, Kumral A, Genc S (2023) Bilirubin induces microglial NLRP3 inflammasome activation in vitro and in vivo. Mol Cell Neurosci 125:103850. https://doi.org/10.1016/j.mcn.2023.103850
doi: 10.1016/j.mcn.2023.103850
pubmed: 36965549
Fiorito F, Marfè G, De Blasio E, Granato GE, Tafani M, De Martino L, Montagnaro S, Florio S, Pagnini U (2008) 2,3,7,8-tetrachlorodibenzo-p-dioxin regulates bovine herpesvirus type 1 induced apoptosis by modulating Bcl-2 family members. Apoptosis 13(10):1243–1252. https://doi.org/10.1007/s10495-008-0249-y
doi: 10.1007/s10495-008-0249-y
pubmed: 18696228
Fiorito F, Iovane V, Cantiello A, Marullo A, De Martino L, Iovane G (2017) MG-132 reduces virus release in bovine herpesvirus-1 Infection. Sci Rep 7(1):13306. https://doi.org/10.1038/s41598-017-13717-1
doi: 10.1038/s41598-017-13717-1
pubmed: 29042667
pmcid: 5645422
Fu X, Chen D, Ma Y, Yuan W, Zhu L (2019a) Bovine Herpesvirus 1 Productive Infection Led to Inactivation of Nrf2 Signaling through Diverse Approaches. Oxid Med Cell Longev, 2019, 4957878. https://doi.org/10.1155/2019/4957878
Fu X, Jiang X, Chen X, Zhu L, Zhang G (2019b) The Differential Expression of Mitochondrial Function-Associated Proteins and Antioxidant Enzymes during Bovine Herpesvirus 1 Infection: A Potential Mechanism for Virus Infection-Induced Oxidative Mitochondrial Dysfunction. Mediators Inflamm, 2019, 7072917. https://doi.org/10.1155/2019/7072917
Gao R, Zhang Y, Kang Y, Xu W, Jiang L, Guo T, Huan C (2020) Glycyrrhizin inhibits PEDV Infection and Proinflammatory Cytokine Secretion via the HMGB1/TLR4-MAPK p38 pathway. Int J Mol Sci 21(8). https://doi.org/10.3390/ijms21082961
Gou H, Chen X, Zhu X, Li L, Hou L, Zhou Y, Xu Y (2022) Sequestered SQSTM1/p62 crosstalk with Keap1/NRF2 axis in hPDLCs promotes oxidative stress injury induced by periodontitis. Free Radic Biol Med 190:62–74. https://doi.org/10.1016/j.freeradbiomed.2022.08.001
doi: 10.1016/j.freeradbiomed.2022.08.001
pubmed: 35940517
Guan X, Shen S, Liu J, Song H, Chang J, Mao X, Song J, Zhang L, Liu C (2023) Protective effecs of baicalin magnesium on non-alcoholic steatohepatitis rats are based on inhibiting NLRP3/Caspase-1/IL-1β signaling pathway. BMC Complement Med Ther 23(1):72. https://doi.org/10.1186/s12906-023-03903-2
doi: 10.1186/s12906-023-03903-2
pubmed: 36879310
pmcid: 9987046
Jain S, Saha P, Syamprasad NP, Panda SR, Rajdev B, Jannu AK, Sharma P, Naidu VGM (2023) Targeting TLR4/3 using chlorogenic acid ameliorates LPS + POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stress-mediated NLRP3/NF-κB axis. Clin Sci (Lond) 137(10):785–805. https://doi.org/10.1042/cs20220625
doi: 10.1042/cs20220625
pubmed: 36951146
Jiao K, Su P, Li Y (2023) FGFR2 modulates the Akt/Nrf2/ARE signaling pathway to improve angiotensin II-induced hypertension-related endothelial dysfunction. Clin Exp Hypertens 45(1):2208777. https://doi.org/10.1080/10641963.2023.2208777
doi: 10.1080/10641963.2023.2208777
pubmed: 37154169
Jing H, Wang F, Gao XJ (2022) Lithium intoxication induced pyroptosis via ROS/NF-κB/NLRP3 inflammasome regulatory networks in kidney of mice. Environ Toxicol 37(4):825–835. https://doi.org/10.1002/tox.23446
doi: 10.1002/tox.23446
pubmed: 34984798
Li C, Han P, Mao H, Lv C, Huang K, Jin M (2023) Glycyrrhizic acid-based carbonized dots boost antiviral activity against Influenza A Virus via Multisite Inhibition mechanisms. ACS Appl Mater Interfaces 15(8):10441–10451. https://doi.org/10.1021/acsami.2c21319
doi: 10.1021/acsami.2c21319
pubmed: 36789721
Liang J, Gao Y, Feng Z, Zhang B, Na Z, Li D (2023) Reactive oxygen species and ovarian Diseases: antioxidant strategies. Redox Biol 62:102659. https://doi.org/10.1016/j.redox.2023.102659
doi: 10.1016/j.redox.2023.102659
pubmed: 36917900
pmcid: 10023995
Ling LJ, Lu Y, Zhang YY, Zhu HY, Tu P, Li H, Chen DF (2020) Flavonoids from Houttuynia cordata attenuate H1N1-induced acute lung injury in mice via inhibition of Influenza virus and toll-like receptor signalling. Phytomedicine 67:153150. https://doi.org/10.1016/j.phymed.2019.153150
doi: 10.1016/j.phymed.2019.153150
pubmed: 31958713
Liu Y, Zhang Q, Zou M, Cui J, Shi X, Li L, Wu F, Xu X (2023) Cell entry of bovine herpesvirus-1 through clathrin- and caveolin-mediated endocytosis requires activation of PI3K-Akt-NF-κB and Ras-p38 MAPK pathways as well as the interaction of BoHV-1 gD with cellular receptor nectin-1. Vet Microbiol 279:109672. https://doi.org/10.1016/j.vetmic.2023.109672
doi: 10.1016/j.vetmic.2023.109672
pubmed: 36774841
Marin M, Rensetti D, Burucúa M, Rosales JJ, Cuesta LM, Pérez S (2023) Microscopic lesions and modulation of gene expression in cervical medulla during BoAHV-1and BoAHV-5 Infection: a mini-review. Res Vet Sci 156:81–87. https://doi.org/10.1016/j.rvsc.2023.02.002
doi: 10.1016/j.rvsc.2023.02.002
pubmed: 36791580
Meng L, Wang M, Gao Y, Chen L, Wang K, Gao W, Liu Q (2023) Dopamine D1 receptor agonist alleviates acute lung injury via modulating inflammatory responses in macrophages and barrier function in airway epithelial cells. Free Radic Biol Med 202:2–16. https://doi.org/10.1016/j.freeradbiomed.2023.03.016
doi: 10.1016/j.freeradbiomed.2023.03.016
pubmed: 36965538
pmcid: 10033496
Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, Doerr HW, Cinatl J (2011) Glycyrrhizin exerts antioxidative effects in H5N1 Influenza a virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS ONE 6(5):e19705. https://doi.org/10.1371/journal.pone.0019705
doi: 10.1371/journal.pone.0019705
pubmed: 21611183
pmcid: 3096629
Muylkens B, Thiry J, Kirten P, Schynts F, Thiry E (2007) Bovine herpesvirus 1 Infection and infectious bovine rhinotracheitis. Vet Res 38(2):181–209. https://doi.org/10.1051/vetres:2006059
doi: 10.1051/vetres:2006059
pubmed: 17257569
N’Jai A, Rivera U, Atapattu J, Owusu-Ofori DN, Czuprynski K, C J (2013) Gene expression profiling of bovine bronchial epithelial cells exposed in vitro to bovine herpesvirus 1 and Mannheimia haemolytica. Vet Immunol Immunopathol 155(3):182–189. https://doi.org/10.1016/j.vetimm.2013.06.012
doi: 10.1016/j.vetimm.2013.06.012
pubmed: 23890750
pmcid: 7127263
Perez S, Inman M, Doster A, Jones C (2005) Latency-related gene encoded by bovine herpesvirus 1 promotes virus growth and reactivation from latency in tonsils of infected calves. J Clin Microbiol 43(1):393–401. https://doi.org/10.1128/jcm.43.1.393-401.2005
doi: 10.1128/jcm.43.1.393-401.2005
pubmed: 15635000
pmcid: 540132
Pérez Gaudio D, Pérez S, Mozo J, Martínez G, Decundo J, Dieguez S, Soraci A (2023) Fosfomycin modifies the replication kinetics of bovine alphaherpesvirus-1 and reduces the timing of its protein expression on bovine (MDBK) and human (SH-SY5Y) cell lines. Vet Res Commun. https://doi.org/10.1007/s11259-023-10150-w
doi: 10.1007/s11259-023-10150-w
pubmed: 37328643
Shan C, Xiong Y, Miao F, Liu T, Akhtar RW, Shah SAH, Gao H, Zhu E, Cheng Z (2023) Hydroxytyrosol mitigates Mycoplasma gallisepticum-induced pulmonary injury through downregulation of the NF-κB/NLRP3/IL-1β signaling pathway in chicken. Poult Sci 102(5):102582. https://doi.org/10.1016/j.psj.2023.102582
doi: 10.1016/j.psj.2023.102582
pubmed: 36940652
pmcid: 10033309
Shi S, Chen Y, Luo Z, Nie G, Dai Y (2023) Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy. Cell Commun Signal 21(1):61. https://doi.org/10.1186/s12964-023-01077-5
doi: 10.1186/s12964-023-01077-5
pubmed: 36918950
pmcid: 10012797
Tafuri S, Marullo A, Ciani F, Della Morte R, Montagnaro S, Fiorito F, De Martino L (2018) Reactive oxygen metabolites in alpha-herpesvirus-seropositive Mediterranean buffaloes (Bubalus bubalis): a preliminary study. Pol J Vet Sci 21(3):639–642. https://doi.org/10.24425/124300
doi: 10.24425/124300
pubmed: 30468352
Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM (1996) Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 274(5288):787–789. https://doi.org/10.1126/science.274.5288.787
doi: 10.1126/science.274.5288.787
pubmed: 8864120
van de Sand L, Bormann M, Alt M, Schipper L, Heilingloh CS, Steinmann E, Todt D, Dittmer U, Elsner C, Witzke O, Krawczyk A (2021) Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease. Viruses 13(4). https://doi.org/10.3390/v13040609
Wang J, Alexander J, Wiebe M, Jones C (2014) Bovine herpesvirus 1 productive Infection stimulates inflammasome formation and caspase 1 activity. Virus Res 185:72–76. https://doi.org/10.1016/j.virusres.2014.03.006
doi: 10.1016/j.virusres.2014.03.006
pubmed: 24657787
Wang J, Ren C, Bi W, Batu W (2023a) Glycyrrhizin mitigates acute lung injury by inhibiting the NLRP3 inflammasome in vitro and in vivo. J Ethnopharmacol 303:115948. https://doi.org/10.1016/j.jep.2022.115948
doi: 10.1016/j.jep.2022.115948
pubmed: 36423713
Wang LH, Gu ZW, Li J, Yang WQ, Li YL, Qi DM, Wang DY, Jiang HQ (2023b) Isorhynchophylline inhibits inflammatory responses in endothelial cells and macrophages through the NF-κB/NLRP3 signaling pathway. BMC Complement Med Ther 23(1):80. https://doi.org/10.1186/s12906-023-03902-3
doi: 10.1186/s12906-023-03902-3
pubmed: 36906555
pmcid: 10007741
Wang Y, Fang D, Yang Q, You J, Wang L, Wu J, Zeng M, Luo M (2023c) Interactions between PCSK9 and NLRP3 inflammasome signaling in Atherosclerosis. Front Immunol 14:1126823. https://doi.org/10.3389/fimmu.2023.1126823
doi: 10.3389/fimmu.2023.1126823
pubmed: 36911736
pmcid: 9992811
Wang Z, Zhang H, Qi C, Guo H, Jiao X, Yan J, Wang Y, Li Q, Zhao M, Guo X, Wan B, Li X (2023d) Ursolic acid ameliorates DNCB-induced atopic dermatitis-like symptoms in mice by regulating TLR4/NF-κB and Nrf2/HO-1 signaling pathways. Int Immunopharmacol 118:110079. https://doi.org/10.1016/j.intimp.2023.110079
doi: 10.1016/j.intimp.2023.110079
pubmed: 36996741
Winkler MT, Doster A, Jones C (2000) Persistence and reactivation of bovine herpesvirus 1 in the tonsils of latently infected calves. J Virol 74(11):5337–5346. https://doi.org/10.1128/jvi.74.11.5337-5346.2000
doi: 10.1128/jvi.74.11.5337-5346.2000
pubmed: 10799611
pmcid: 110889
Wu H, Wang Y, Fu H, Ji L, Li N, Zhang D, Su L, Hu Z (2023) Maresin1 ameliorates Sepsis-Induced Microglial Neuritis Induced through blocking TLR4-NF-κ B-NLRP3 signaling pathway. J Pers Med 13(3). https://doi.org/10.3390/jpm13030534
Xu X, Zhang K, Huang Y, Ding L, Chen G, Zhang H, Tong D (2012) Bovine herpes virus type 1 induces apoptosis through Fas-dependent and mitochondria-controlled manner in Madin-Darby bovine kidney cells. Virol J 9:202. https://doi.org/10.1186/1743-422x-9-202
doi: 10.1186/1743-422x-9-202
pubmed: 22978358
pmcid: 3502331
Xu H, Fang L, Zeng Q, Chen J, Ling H, Xia H, Ge Q, Wu C, Zou K, Wang X, Wang P, Yuan W, Dong R, Hu S, Xiao L, He B, Tong P, Jin H (2023) Glycyrrhizic acid alters the hyperoxidative stress-induced differentiation commitment of MSCs by activating the Wnt/β-catenin pathway to prevent SONFH. Food Funct 14(2):946–960. https://doi.org/10.1039/d2fo02337g
doi: 10.1039/d2fo02337g
pubmed: 36541285
Ye Y, Zhou J (2023) The protective activity of natural flavonoids against osteoarthritis by targeting NF-κB signaling pathway. Front Endocrinol (Lausanne) 14:1117489. https://doi.org/10.3389/fendo.2023.1117489
doi: 10.3389/fendo.2023.1117489
pubmed: 36998478
Yesilbag K, Toker EB, Ates O (2021) Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro. Virus Res 297:198384. https://doi.org/10.1016/j.virusres.2021.198384
doi: 10.1016/j.virusres.2021.198384
pubmed: 33713753
Yuan C, Fu X, Huang L, Ma Y, Ding X, Zhu L, Zhu G (2016) The synergistic antiviral effects of GSH in combination with acyclovir against BoHV-1 Infection in vitro. Acta Virol 60(3):328–332. https://doi.org/10.4149/av_2016_03_328
doi: 10.4149/av_2016_03_328
pubmed: 27640443
Zhang B, Qi F (2023) Herbal medicines exhibit a high affinity for ACE2 in treating COVID-19. Biosci Trends 17(1):14–20. https://doi.org/10.5582/bst.2022.01534
doi: 10.5582/bst.2022.01534
pubmed: 36596560
Zhang C, Li C, Shao Q, Meng S, Wang X, Kong T, Li Y (2023) Antioxidant monoammonium glycyrrhizinate alleviates damage from oxidative stress in perinatal cows. J Anim Physiol Anim Nutr (Berl) 107(2):475–484. https://doi.org/10.1111/jpn.13764
doi: 10.1111/jpn.13764
pubmed: 35989475
Zhu L, Yuan C, Zhang D, Ma Y, Ding X, Zhu G (2016) BHV-1 induced oxidative stress contributes to mitochondrial dysfunction in MDBK cells. Vet Res 47:47. https://doi.org/10.1186/s13567-016-0332-2
doi: 10.1186/s13567-016-0332-2
pubmed: 27000063
pmcid: 4802597
Zhu L, Fu X, Yuan C, Jiang X, Zhang G (2018) Induction of oxidative DNA damage in bovine herpesvirus 1 infected bovine kidney cells (MDBK cells) and human Tumor cells (A549 cells and U2OS cells). Viruses 10(8). https://doi.org/10.3390/v10080393
Zhu WT, Li CH, Dai TT, Song QQ, Chen Y, Han ZL, Sun NX, Wang DL (2023) Effect of allyl isothiocyanate on oxidative stress in COPD via the AhR / CYP1A1 and Nrf2 / NQO1 pathways and the underlying mechanism. Phytomedicine 114:154774. https://doi.org/10.1016/j.phymed.2023.154774
doi: 10.1016/j.phymed.2023.154774
pubmed: 36996530
Zuo X, Zeng H, Wang B, Yang X, He D, Wang L, Ouyang H, Yuan J (2022) AKR1C1 protects corneal epithelial cells against oxidative stress-mediated ferroptosis in Dry Eye. Invest Ophthalmol Vis Sci 63(10):3. https://doi.org/10.1167/iovs.63.10.3
doi: 10.1167/iovs.63.10.3
pubmed: 36066316
pmcid: 9463717