Ferroptosis is involved in acetaminophen induced cell death
Abstract
The recently described form of programmed cell death, ferroptosis can be induced by agents causing GSH depletion or the inhibition of GPX4. Ferroptosis clearly shows distinct morphologic, biochemical and genetic features from apoptosis, necrosis and autophagy. Since NAPQI the highly reactive metabolite of the widely applied analgesic and antipyretic, acetaminophen induces a cell death which can be characterized by GSH depletion, GPX inhibition and caspase independency the involvement of ferroptosis in acetaminophen induced cell death has been investigated. The specific ferroptosis inhibitor ferrostatin-1 failed to elevate the viability of acetaminophen treated HepG2 cells. It should be noticed that these cells do not form NAPQI due to the lack of phase I enzyme expression therefore GSH depletion cannot be observed. However in the case of acetaminophen treated primary mouse hepatocytes the significant elevation of cell viability could be observed upon ferrostatin-1 treatment. Similar to ferrostatin-1 treatment, the addition of the RIP1 kinase inhibitor necrostatin-1 could also elevate the viability of acetaminophen treated primary hepatocytes. Ferrostatin-1 has no influence on the expression of CYP2E1 or on the cellular GSH level which suggest that the protective effect of ferrostatin-1 in APAP induced cell death is not based on the reduced metabolism of APAP to NAPQI or on altered NAPQI conjugation by cellular GSH. Our results suggest that beyond necroptosis and apoptosis a third programmed cell death, ferroptosis is also involved in acetaminophen induced cell death in primary hepatocytes.
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Acetaminophen induces ferroptosis in primary hepatocytes through glutathione depletion, suggesting a mechanism of drug-induced toxicity.
“Acetaminophen has been reported to induce ferroptosis in primary hepatocytes via glutathione depletion [40], suggesting this may be a mechanism of drug-induced toxicity.”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [40]
Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · see citing works
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713 · see citing works
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732 · see citing works
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
Identification of RIP1 kinase as a specific cellular target of necrostatins
Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.83 · Cited by 2,059 · see citing works
ACETAMINOPHEN-INDUCED HEPATIC NECROSIS. IV. PROTECTIVE ROLE OF GLUTATHIONE
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., & Brodie, B. B. (1973) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29666-5 · Cited by 1,737 · see citing works
ACETAMINOPHEN-INDUCED HEPATIC NECROSIS. I. ROLE OF DRUG METABOLISM
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Davis, D. C., Gillette, J. R., & Brodie, B. B. (1973) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29663-x · Cited by 1,498 · see citing works
Acetaminophen-Induced Hepatic Necrosis
Jollow, D. J., Thorgeirsson, S. S., Potter, W. Z., Hashimoto, M., & Mitchell, J. R. (2008) · Pharmacology · doi:10.1159/000136547 · Cited by 1,091 · see citing works
Murphy, T. H., Miyamoto, M., Sastre, A., Schnaar, R. L., & COYLE, J. T. (1989) · Neuron · doi:10.1016/0896-6273(89)90043-3 · Cited by 1,033 · see citing works
Jaeschke, H., McGill, M. R., & Ramachandran, A. (2012) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.602688 · Cited by 972 · see citing works
McGill, M. R., Williams, C. D., Xie, Y., Ramachandran, A., & Jaeschke, H. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.08.015 · Cited by 421 · see citing works
Glutathione, ascorbate, and cellular protection.
Meister, A. (1994) · PubMed · Cited by 421 · see citing works
Mode of Cell Death after Acetaminophen Overdose in Mice: Apoptosis or Oncotic Necrosis?
Gujral, J. (2002) · Toxicological Sciences · doi:10.1093/toxsci/67.2.322 · Cited by 421 · see citing works
HepaRG Cells: A Human Model to Study Mechanisms of Acetaminophen Hepatotoxicity Δσ
McGill, M. R., Yan, H., Ramachandran, A., Murray, G. J., Rollins, D. E., & Jaeschke, H. (2010) · Hepatology · doi:10.1002/hep.24132 · Cited by 292 · see citing works
Ascorbic acid recycling in human neutrophils
Washko, P., Wang, Y., & Levine, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82289-x · Cited by 289 · see citing works
McGill, M. R., Lebofsky, M., Norris, H.-R. K., Slawson, M. H., Bajt, M. L., Xie, Y., Williams, C. D., Wilkins, D. G., Rollins, D. E., & Jaeschke, H. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.03.026 · Cited by 241 · see citing works
Jaeschke, H., McGill, M. R., Williams, C. D., & Ramachandran, A. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.01.025 · Cited by 230 · see citing works
Lawson, J. A., Fisher, M. A., Simmons, C. A., Farhood, A. I., & Jaeschke, H. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8635 · Cited by 162 · see citing works
Role of caspase-1 and interleukin-1β in acetaminophen-induced hepatic inflammation and liver injury
Williams, C. D., Farhood, A. I., & Jaeschke, H. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.07.004 · Cited by 157 · see citing works
Tirmenstein, M. A., & Nelson, S. D. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39733-9 · Cited by 153 · see citing works
Takemoto, K., Hatano, E., Iwaisako, K., Takeiri, M., Noma, N., Ohmae, S., Toriguchi, K., Tanabe, K., Tanaka, H., Seo, S., et al. (2014) · FEBS Open Bio · doi:10.1016/j.fob.2014.08.007 · Cited by 151 · see citing works
Zhang, Y.-F., He, W., Zhang, C., Liu, X.-J., Lu, Y., Wang, H., Zhang, Z., Chen, X., & Xu, D. (2014) · Toxicology Letters · doi:10.1016/j.toxlet.2014.01.005 · Cited by 121 · see citing works
Acetaminophen induces ER dependent signaling in mouse liver
Nagy, G., Kardon, T., Wunderlich, L., Szarka, A., Kiss, A., Schaff, Z., Bánhegyi, G., & Mandl, J. (2006) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.11.021 · Cited by 109 · see citing works
Self-citationInterspecies differences in acetaminophen sensitivity of human, rat, and mouse primary hepatocytes
Jemnitz, K., Veres, Z., Monostory, K., Kob́ori, L., & Vereczkey, L. (2008) · Toxicology in Vitro · doi:10.1016/j.tiv.2008.02.001 · Cited by 85 · see citing works
Self-citationHepG2 Cells: An in Vitro Model for P450-Dependent Metabolism of Acetaminophen
Roe, A. L., SNAWDER, J. E., Benson, R. W., Roberts, D. W., & Casciano, D. A. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1003 · Cited by 82 · see citing works
Interaction of Ascorbate and α-Tocopherol in Resealed Human Erythrocyte Ghosts
May, J. M., Qu, Z., & Morrow, J. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.18.10577 · Cited by 81 · see citing works
BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury
Nagy, G., Szarka, A., Lotz, G., Dóczi, J., Wunderlich, L., Kiss, A., Jemnitz, K., Veres, Z., Bánhegyi, G., Schaff, Z., et al. (2009) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.11.017 · Cited by 63 · see citing works
Self-citationN‐Acetylcysteine does not Protect HepG2 Cells against Acetaminophen‐Induced Apoptosis
Manov, I., Hirsh, M., & Iancu, T. C. (2004) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2004.pto940504.x · Cited by 62 · see citing works
Glycogen Synthase Kinase-3 Mediates Acetaminophen-Induced Apoptosis in Human Hepatoma Cells
Macanas-Pirard, P., Yaacob, N.-S., Lee, P. C., Holder, J. C., Hinton, R. H., & Kass, G. E. N. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.081364 · Cited by 43 · see citing works
Maintenance and activation of Cyp2e-1 gene expression in mouse hepatocytes in primary culture
Sakurai, J., Funae, Y., & Nemoto, N. (1996) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(96)00051-1 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ferroptosis: process and function
Xie, Y., Hou, W., Song, X., Yu, Y., Huang, J., Sun, X., Kang, R., & Tang, D. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.158 · Cited by 3,727 · see citing works
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088 · see citing works
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099 · see citing works
Cao, J. Y., & Dixon, S. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2194-1 · Cited by 1,515 · see citing works
The chemical basis of ferroptosis
Conrad, M., & Pratt, D. A. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0408-1 · Cited by 1,027 · see citing works
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Re, D. P. D., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 979 · see citing works
GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues
Maiorino, M., Conrad, M., & Ursini, F. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7115 · Cited by 709 · see citing works
Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators
Kajarabille, N., & Latunde-Dada, G. O. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194968 · Cited by 680 · see citing works
The multifaceted role of ferroptosis in liver disease
Chen, J., Li, X., Ge, C., Min, J., & Wang, F. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00941-0 · Cited by 679 · see citing works
Ferroptosis as a novel therapeutic target for cardiovascular disease
Wu, X., Li, Y., Zhang, S., & Zhou, X. (2021) · Theranostics · doi:10.7150/thno.54113 · Cited by 650 · see citing works
Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells
Ma, S., Henson, E. S., Chen, Y., & Gibson, S. B. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.208 · Cited by 627 · see citing works
Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis
Imai, H., Matsuoka, M., Kumagai, T., Sakamoto, T., & Koumura, T. (2016) · Current topics in microbiology and immunology · doi:10.1007/82_2016_508 · Cited by 629 · see citing works
Targeting ferroptosis opens new avenues for the development of novel therapeutics
Sun, S., Shen, J., Jiang, J., Wang, F., & Min, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01606-1 · Cited by 632 · see citing works
Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs
Su, Y., Zhao, B., Zhou, L., Zhang, Z., Shen, Y., Lv, H., AlQudsy, L. H. H., & Shang, P. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.02.015 · Cited by 580 · see citing works
Regulation of lipid peroxidation and ferroptosis in diverse species
Conrad, M., Kagan, V. E., Bayir, H., Pagnussat, G. C., Head, B., Traber, M. G., & Stockwell, B. R. (2018) · Genes & Development · doi:10.1101/gad.314674.118 · Cited by 544 · see citing works
Molecular mechanisms of ferroptosis and their involvement in brain diseases
Costa, I., Barbosa, D. J., Benfeito, S., Silva, V., Chavarria, D., Borges, F., Remião, F., & Silva, R. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108373 · Cited by 402 · see citing works
Yamada, N., Karasawa, T., Kimura, H. J., Watanabe, S., Komada, T., Kamata, R., Sampilvanjil, A., Ito, J., Nakagawa, K., Kuwata, H., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2334-2 · Cited by 340 · see citing works
Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis
Iorga, A., Dara, L., & Kaplowitz, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18051018 · Cited by 299 · see citing works
Cell Death in Liver Diseases: A Review
Shojaie, L., Iorga, A., & Dara, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249682 · Cited by 299 · see citing works
Eid, R., Arab, N. T. T., & Greenwood, M. T. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.12.002 · Cited by 286 · see citing works
Ferroptosis in liver disease: new insights into disease mechanisms
Wu, J., Wang, Y., Jiang, R., Xue, R., Yin, X., Wu, M., & Meng, Q. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00660-4 · Cited by 287 · see citing works
Ferroptosis and Its Potential Role in Human Diseases
Han, C., Liu, Y., Dai, R., Ismail, N., Su, W., & Li, B. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00239 · Cited by 274 · see citing works
Identification of baicalein as a ferroptosis inhibitor by natural product library screening
Xie, Y., Song, X., Sun, X., Huang, J. L., Zhong, M., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.03.052 · Cited by 246 · see citing works
Liu, B., Zhao, C., Li, H., Chen, X., Ding, Y., & Xu, S. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.02.061 · Cited by 238 · see citing works
Copper signalling: causes and consequences
Kardos, J., Héja, L., Simon, Á., Jablonkai, I., Kovács, R., & Jemnitz, K. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0277-3 · Cited by 214 · see citing works
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Zhao, W., Zhou, Y., Xu, T., & Wu, Q. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9929687 · Cited by 212 · see citing works
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Ru, Q., Li, Y., Xie, W., Ding, Y., Chen, L., Xu, G., Wu, Y., & Wang, F. (2023) · Bone Research · doi:10.1038/s41413-023-00247-y · Cited by 206 · see citing works
Li, D., Liu, X., Pi, W., Zhang, Y., Yu, L., Cheng, X., Sun, Z., & Jiang, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.808480 · Cited by 194 · see citing works
Niu, B., Lei, X., Xu, Q., Ju, Y., Xu, D., Mao, L., Li, J., Zheng, Y., Sun, N., Zhang, X., et al. (2021) · Cell Biology and Toxicology · doi:10.1007/s10565-021-09624-x · Cited by 185 · see citing works
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He, J., Li, Z., Xia, P., Shi, A., FuChen, X., Zhang, J., & Yu, P. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101470 · Cited by 181 · see citing works
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Zheng, H., Jiang, J., Xu, S., Liu, W., Xie, Q., Cai, X., Zhang, J., Liu, S., & Li, R. (2021) · Nanoscale · doi:10.1039/d0nr08478f · Cited by 164 · see citing works
To eat or not to eat — the metabolic flavor of ferroptosis
Gao, M., & Jiang, X. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.11.001 · Cited by 157 · see citing works
Mechanisms of acetaminophen hepatotoxicity and their translation to the human pathophysiology
Ramachandran, A., & Jaeschke, H. (2017) · Journal of Clinical and Translational Research · doi:10.18053/jctres.03.2017s1.002 · Cited by 163 · see citing works
Jiang, M., Qiao, M., Zhao, C., Deng, J., Li, X., & Zhou, C. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-341 · Cited by 157 · see citing works
Drug induced liver injury – a 2023 update
Allison, R., Guraka, A., Shawa, I. T., Tripathi, G., Moritz, W., & Kermanizadeh, A. (2023) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2023.2261848 · Cited by 150 · see citing works
Gai, C., Yu, M., Li, Z., Wang, Y., Ding, D., Zheng, J., Lv, S., Zhang, W., & Li, W. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29221 · Cited by 149 · see citing works
The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?
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Emerging and established modes of cell death during acetaminophen-induced liver injury
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Recent progress on targeting ferroptosis for cancer therapy
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Tang, S., Gao, P., Chen, H., Zhou, X., Ou, Y., & He, Y. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.590789 · Cited by 119 · see citing works
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Wang, M., Liu, C., Wang, T., Yu, H.-M., Ouyang, S., Wu, Y., Gong, H., Ma, X., Jiao, G., Fu, L., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02961-5 · Cited by 116 · see citing works
Macías‐Rodríguez, R. U., Inzaugarat, M. E., Ruiz‐Margáin, A., Nelson, L. J., Trautwein, C., & Cubero, F. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051651 · Cited by 114 · see citing works
Yang, X., Kawasaki, N. K., Min, J., Matsui, T., & Wang, F. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2022.10.004 · Cited by 114 · see citing works
Neuroprotective effect of deferoxamine on erastin-induced ferroptosis in primary cortical neurons
Zhang, Y., Fan, B., Pang, Y.-L., Shen, W., Wang, X., Zhao, C.-X., Li, W.-X., Liu, C., Kong, X.-H., Ning, G.-Z., et al. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.274344 · Cited by 113 · see citing works
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Mishima, E., & Conrad, M. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062320-114541 · Cited by 105 · see citing works
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Shen, L., Lin, D., Li, X., Wu, H., Lenahan, C., Pan, Y., Xu, W., Chen, Y., Shao, A., & Zhang, J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00594 · Cited by 102 · see citing works
Arsenite induces testicular oxidative stress in vivo and in vitro leading to ferroptosis
Meng, P., Zhang, S., Jiang, X., Cheng, S., Zhang, J., Cao, X., Qin, X., Zou, Z., & Chen, C. (2020) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2020.110360 · Cited by 101 · see citing works
Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria
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Cell death in drug-induced liver injury
Iorga, A., & Dara, L. (2019) · Advances in pharmacology · doi:10.1016/bs.apha.2019.01.006 · Cited by 87 · see citing works
Ferroptosis in viral infection: the unexplored possibility
Wang, M., Banda, J., Jin, N., Du, S., & Li, C. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00814-1 · Cited by 90 · see citing works
Mechanism of Ferroptosis: A Potential Target for Cardiovascular Diseases Treatment
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Ferroptosis is associated with oxygen-glucose deprivation/reoxygenation-induced Sertoli cell death
Li, L., Yu, H., Zhao, Y., Wang, H., Zhao, X., Jiang, Y., & Gao, F. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3469 · Cited by 87 · see citing works
Zhang, X., Xing, X., Liu, H., Feng, J., Tian, M., Chang, S., Liu, P., & Zhang, H. (2020) · International Journal of Radiation Biology · doi:10.1080/09553002.2020.1708993 · Cited by 86 · see citing works
Targeting oxidative stress-mediated regulated cell death as a vulnerability in cancer
Chen, D., Guo, Z., Yao, L., Sun, Y., Dian, Y., Zhao, D., Ke, Y., Zeng, F., Zhang, C., Deng, G., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103686 · Cited by 88 · see citing works
Iron metabolism and ferroptosis in human health and disease
Zhong, M., Wang, Y., Min, J., & Wang, F. (2025) · BMC Biology · doi:10.1186/s12915-025-02378-6 · Cited by 86 · see citing works
Aizawa, S., Brar, G., & Tsukamoto, H. (2019) · Gut and Liver · doi:10.5009/gnl18486 · Cited by 77 · see citing works
Javadov, S. A. (2022) · Current Opinion in Physiology · doi:10.1016/j.cophys.2022.100483 · Cited by 77 · see citing works
Yang, W. P., Liu, X., Song, C., Ji, S., Yang, J., Liu, Y., You, J., Zhang, J., Huang, S., Cheng, W., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112842 · Cited by 77 · see citing works
Protective effect of sestrin2 against iron overload and ferroptosis-induced liver injury
Park, S. J., Cho, S. S., Kim, K. M., Yang, J. H., Kim, J., Jeong, E. H., Yang, J. W., Han, C. Y., Ku, S., Cho, I. J., et al. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114665 · Cited by 75 · see citing works
Ferroptosis and its role in cardiomyopathy
Li, D., Pi, W., Sun, Z., Liu, X., & Jiang, J. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113279 · Cited by 72 · see citing works
Zeng, T., Deng, G., Zhong, W., Gao, Z., Ma, S., Mo, C., Li, Y., Huang, S., Zhou, C., Lai, Y., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.01.009 · Cited by 71 · see citing works
Ferroptosis-related small-molecule compounds in cancer therapy: Strategies and applications
Yin, L., Liu, P., Jin, Y., Ning, Z., Yang, Y., & Gao, H. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114861 · Cited by 66 · see citing works
Li, S., Dong, C., Geng, D., He, Q., & Shi, Y. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.07.081 · Cited by 65 · see citing works
Honokiol induces ferroptosis in colon cancer cells by regulating GPX4 activity.
Guo, C., Liu, P., Deng, G., Han, Y., Chen, Y., Cai, C., Shen, H., Deng, G., & Zeng, S. (2021) · PubMed Central · Cited by 64 · see citing works
Ferroptosis is Involved in Hypoxic-ischemic Brain Damage in Neonatal Rats
Lin, W., Zhang, T., Zheng, J., Zhou, Y., Lin, Z., & Fu, X. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.02.013 · Cited by 64 · see citing works
Ferroptosis as a new therapeutic opportunity for nonviral liver disease
Jia, M., Zhang, H., Qin, Q., Hou, Y., Zhang, X., Chen, D., Zhang, H., & Chen, Y. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174319 · Cited by 62 · see citing works
Non-classical ferroptosis inhibition by a small molecule targeting PHB2
Yang, W. P., Mu, B., You, J., Tian, C., Bin, H., Xu, Z., Zhang, L., Ma, R., Wu, M., Zhang, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35294-2 · Cited by 62 · see citing works
Ferroptosis: The Entanglement between Traditional Drugs and Nanodrugs in Tumor Therapy
Liu, K., Huang, L., Qi, S., Liu, S., Xie, W., Du, L., Jing, C., Zhang, X., Zhang, B., Liu, L., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202203085 · Cited by 59 · see citing works
Pan, Y., Tang, P., Cao, J., Song, Q. H., Zhu, L., Ma, S., & Zhang, J. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.09.140 · Cited by 51 · see citing works
The interplay of autophagy and non-apoptotic cell death pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.12.004 · Cited by 50 · see citing works
Differences in hepatocellular iron metabolism underlie sexual dimorphism in hepatocyte ferroptosis
Tao, H., Dar, H. Y., Tian, C. L., Banerjee, S., Glazer, E. S., Srinivasan, S., Zhu, L., Pacifici, R., & He, P. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102892 · Cited by 50 · see citing works
Sze, S. C. W., Zhang, L., Zhang, S., Lin, K., Ng, T. B., Ng, M. L., Lee, C., Lam, J. K. W., Zhang, Z., & Yung, K. K. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012689 · Cited by 47 · see citing works
Zhang, H., Shi, H., Li, X., Zhou, S., Song, X., Ma, N., Meng, M., Chang, G., & Shen, X. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103557 · Cited by 46 · see citing works
Ferroptosis and Acetaminophen Hepatotoxicity: Are We Going Down Another Rabbit Hole?
Jaeschke, H., Adelusi, O. B., & Ramachandran, A. (2021) · Gene Expression · doi:10.3727/105221621x16104581979144 · Cited by 44 · see citing works
Matrine disrupts Nrf2/GPX4 antioxidant system and promotes hepatocyte ferroptosis
Wang, X., Zhu, W., Xing, M., Zhu, H., Chen, E., & Zhou, J. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110713 · Cited by 42 · see citing works
Treatment of Drug-Induced Liver Injury
Teschke, R. (2022) · Biomedicines · doi:10.3390/biomedicines11010015 · Cited by 41 · see citing works
Research mechanisms of and pharmaceutical treatments for ferroptosis in liver diseases
Yu, J. G., & Wang, J. (2020) · Biochimie · doi:10.1016/j.biochi.2020.11.002 · Cited by 40 · see citing works
Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases
Arumugam, M. K., Gopal, T., Kandy, R. R. K., Boopathy, L. K., Perumal, S. K., Ganesan, M., Rasineni, K., Donohue, T. M., Osna, N. A., & Kharbanda, K. K. (2023) · Biology · doi:10.3390/biology12101311 · Cited by 38 · see citing works
Atractylodin may induce ferroptosis of human hepatocellular carcinoma cells
He, Y., Fang, D., Liang, T., Pang, H., Nong, Y., Tang, L.-B., Yang, Z., Lu, C., Han, X., Zhao, S., et al. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-4386 · Cited by 38 · see citing works
Iron as a therapeutic target in chronic liver disease
Kouroumalis, E., Tsomidis, I., & Voumvouraki, A. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i4.616 · Cited by 40 · see citing works
Ferroptosis: Biology and Role in Gastrointestinal Disease
Escuder‐Rodríguez, J.-J., Liang, D., Jiang, X., & Sinicrope, F. A. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.01.051 · Cited by 37 · see citing works
Therapeutic Implications of Ferroptosis in Renal Fibrosis
Zhang, Y., Mou, Y., Zhang, J., Suo, C., Zhou, H., Gu, M. J., Wang, Z., & Tan, R. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.890766 · Cited by 37 · see citing works
Renal tubular epithelial cells injury induced by mannitol and its potential mechanism
Shi, J., Qian, J., Li, H., Luo, H., Luo, W., & Lin, Z. (2018) · Renal Failure · doi:10.1080/0886022x.2017.1419973 · Cited by 36 · see citing works
Potential mechanism of ferroptosis in pancreatic cancer (Review)
Chen, G., Guo, G., Zhou, X., & Chen, H. (2019) · Oncology Letters · doi:10.3892/ol.2019.11159 · Cited by 36 · see citing works
Liu, Q., Wang, J., Gu, Z., Ouyang, T., Gao, H., Kan, H., & Yang, Y. (2024) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x24500435 · Cited by 36 · see citing works
The Interrelationship of Pharmacologic Ascorbate Induced Cell Death and Ferroptosis
Lőrincz, T., Holczer, M., Kapuy, O., & Szarka, A. (2018) · Pathology & Oncology Research · doi:10.1007/s12253-018-0539-9 · Cited by 34 · see citing works
Self-citationFerroptosis: A mixed blessing for infectious diseases
Xiao, L.-Y., Huang, H., Fan, S., Zheng, B., Wu, J., Zhang, J., Pi, J., & Xu, J.-F. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.992734 · Cited by 34 · see citing works
Li, J., Lu, Q., Peng, M., Liao, J., Zhang, B., Yang, D., Huang, P., Yang, Y., Zhao, Q., Han, B., et al. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.116069 · Cited by 34 · see citing works
The determination of hepatic glutathione at tissue and subcellular level
Lőrincz, T., & Szarka, A. (2017) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2017.05.004 · Cited by 33 · see citing works
Self-citationWang, L., Huang, H., Li, X., Ouyang, L., Wei, X., Xie, J., Liu, D., Tan, P., & Hu, Z. (2023) · Chinese Medicine · doi:10.1186/s13020-023-00838-1 · Cited by 32 · see citing works
Novel Emerging Mechanisms in Acetaminophen ( APAP ) Hepatotoxicity
Gutierrez, A. H., Goikoetxea‐Usandizaga, N., Sanz‐García, C., Martínez‐Chantar, M. L., & Cubero, F. J. (2024) · Liver International · doi:10.1111/liv.16167 · Cited by 32 · see citing works
Is Ferroptosis a Future Direction in Exploring Cryptococcal Meningitis?
Xu, X., Lin, D., Tu, S., Gao, S., Shao, A., & Sheng, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.598601 · Cited by 32 · see citing works
Ferroptosis: Shedding Light on Mechanisms and Therapeutic Opportunities in Liver Diseases
You, H., Wang, L., Bu, F., Meng, H., Huang, C., Fang, G.-Y., & Li, J. (2022) · Cells · doi:10.3390/cells11203301 · Cited by 32 · see citing works
Efferocytosis in liver disease
Shi, H., Moore, M. P., Wang, X., & Tabas, I. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2023.100960 · Cited by 30 · see citing works
The potential role of acrolein in plant ferroptosis-like cell death
Hajdinák, P., Czobor, Á., & Szarka, A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0227278 · Cited by 30 · see citing works
Self-citationInvolvement of REV-ERBα dysregulation and ferroptosis in aristolochic acid I-induced renal injury
Wang, Y., Wang, Z., Wu, Z., Chen, M., Dong, D., Yu, P., Lu, D., & Wu, B. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114807 · Cited by 30 · see citing works
Wang, Y., Peng, X., Zhang, M., Jia, Y., Yu, B., & Tian, J. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/9738143 · Cited by 29 · see citing works
Pan, J. H., Cha, H., Tang, J., Lee, S., Lee, S. H., Le, B., Redding, M. C., Kim, S., Batish, M., Kong, B. C., et al. (2020) · Food & Function · doi:10.1039/d0fo02286a · Cited by 29 · see citing works
Luo, Y., Chen, H., Liu, H., Jia, W., Yan, J., Ding, W., Zhang, Y., Xiao, Z., & Zhu, Z. (2020) · PubMed Central · Cited by 28 · see citing works
- Authors
- Lőrincz, T., Jemnitz, K., Kardon, T., Mandl, J., & Szarka, A.
- Affiliations
- Budapest University of Technology and Economics (HU)
- Hungarian Academy of Sciences (HU)
- Semmelweis University (HU)
- Corresponding author
- Szarka, András
- Venue
- Pathology & Oncology Research
- Published
- 2015-05-12
- Volume
- 21
- Issue
- 4
- Pages
- 1115-1121
- ISSN
- 1219-4956 (ISSN-L)
- 1532-2807
- OpenAlex
- W657288929
- Cited by
- 219
- References
- 30
- Citations by year
- 2026: 8 · 2025: 32 · 2024: 29 · 2023: 26 · 2022: 29 · 2021: 24 · 2020: 25 · 2019: 19 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 1
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pathology & Oncology Research (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Semmelweis University Repository (Semmelweis University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- ferroptosis, acetaminophen hepatotoxicity, N-acetyl-p-benzoquinone imine, glutathione depletion, GPX4, ferrostatin-1, necrostatin-1, RIP1 kinase, programmed cell death, primary hepatocytes, HepG2 cells, CYP2E1
- MeSH terms
- Acetaminophen, Animals, Cell Survival, Cyclohexylamines, Glutathione, Glutathione Peroxidase, Humans, Imidazoles, Imines, Indoles, Male, Phenylenediamines, Benzoquinones, Cell Death, Apoptosis, Cytochrome P-450 CYP2E1, GTPase-Activating Proteins, Hepatocytes, Cell Line, Tumor, Mice, Hep G2 Cells
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