Resveratrol Induces Pro-Oxidant Effects and Time-Dependent Resistance to Cytotoxicity in Activated Hepatic Stellate Cells
Abstract
Resveratrol (RSV) is known for its antioxidant properties; however, this compound has been proposed to have cytotoxic and pro-oxidant effects depending on its concentration and time of exposure. We previously reported the cell cycle arrest effect of low doses of RSV in GRX cells, an activated hepatic stellate cell model. Here, we evaluated the effects of RSV treatment (0.1-50 μM) for 24 and 120 h on GRX viability and oxidative status. Only treatment with 50 μM of RSV reduced the amount of live cells. However, even low doses of RSV induced an increased reactive species production at both treatment times. While being diminished within 24 h, RSV induced an increase in the SOD activity in 120 h. The cellular damage was substantially increased at 24 h in the 50 μM RSV-treated group, as indicated by the high lipoperoxidation, which may be related to the significant cell death and low proliferation. Paradoxically, this cellular damage and lipoperoxidation were considerably reduced in this group after 120 h of treatment while the surviving cells proliferated. In conclusion, RSV induced a dose-dependent pro-oxidant effect in GRX cells. The highest RSV dose induced oxidative-related damage, drastically reducing cell viability; but this cytotoxicity seems to be attenuated during 120 h of treatment.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some studies have highlighted RSV's ability to also act as a pro-oxidant molecule, and this dual role depends upon cell type, used dosage, and exposure time.
“Although RSV’s antioxidant properties have been widely demonstrated, some studies [349,350] have highlighted its ability to also act as a pro-oxidant molecule. This dual role depends upon cell type, used dosage, and exposure time [336].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [350]
Cites
Aebi, H. (1984) · Methods in Enzymology · doi:10.1016/s0076-6879(84)05016-3 · Cited by 25,696 · see citing works
New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening
Skehan, P., Storeng, R., Scudiero, D. A., Monks, A. P., McMahon, J., Vistica, D. T., Warren, J. T., Bokesch, H. R., Kenney, S., & Boyd, M. R. (1990) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/82.13.1107 · Cited by 9,801 · see citing works
Misra, H. P., & Fridovich, I. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)45228-9 · Cited by 9,097 · see citing works
[43] Malondialdehyde determination as index of lipid Peroxidation
Draper, H. H., & Hadley, M. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)86135-i · Cited by 4,291 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Current Protocols in Immunology
(2018) · Current Protocols in Immunology · doi:10.1002/(issn)1934-368x · Cited by 3,574 · see citing works
Hansen, M., Nielsen, S. E., & Berg, K. (1989) · Journal of Immunological Methods · doi:10.1016/0022-1759(89)90397-9 · Cited by 3,488 · see citing works
Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver
Friedman, S. L. (2008) · Physiological Reviews · doi:10.1152/physrev.00013.2007 · Cited by 2,842 · see citing works
Mechanisms of Hepatic Fibrogenesis
Friedman, S. L. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.003 · Cited by 2,640 · see citing works
Glutathione: overview of its protective roles, measurement, and biosynthesis
Forman, H. J., Zhang, H., & Rinna, A. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.006 · Cited by 2,636 · see citing works
Trypan Blue Exclusion Test of Cell Viability
Strober, W. (2015) · Current Protocols in Immunology · doi:10.1002/0471142735.ima03bs111 · Cited by 2,623 · see citing works
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280 · see citing works
International Journal of Molecular Medicine
(2026) · International Journal of Molecular Medicine · doi:10.3892/ijmm · Cited by 2,247 · see citing works
Halliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238 · see citing works
Smithers, D. W. (1956) · The Lancet · doi:10.1016/s0140-6736(56)91184-9 · Cited by 1,796 · see citing works
Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata, H., Inohara, H., Kubo, T., & Tsujimoto, Y. (2005) · Nature · doi:10.1038/nature03317 · Cited by 1,635 · see citing works
Trypan Blue Exclusion Test of Cell Viability
Strober, W. (1997) · Current Protocols in Immunology · doi:10.1002/0471142735.ima03bs21 · Cited by 1,349 · see citing works
Review of the folin phenol protein quantitation method of lowry, rosebrough, farr and randall
Peterson, G. L. (1979) · Analytical Biochemistry · doi:10.1016/0003-2697(79)90222-7 · Cited by 1,147 · see citing works
Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy
Barrera, G. (2012) · ISRN Oncology · doi:10.5402/2012/137289 · Cited by 822 · see citing works
Kubli, D. A., & Gustafsson, Å. B. (2012) · Circulation Research · doi:10.1161/circresaha.112.265819 · Cited by 792 · see citing works
Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications
Alarcón‐de‐la‐Lastra, C., & Villegas, I. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351156 · Cited by 740 · see citing works
History, Heterogeneity, Developmental Biology, and Functions of Quiescent Hepatic Stellate Cells
Geerts, A. (2001) · Seminars in Liver Disease · doi:10.1055/s-2001-17550 · Cited by 740 · see citing works
Metabolism and bioavailability oftrans-resveratrol
Wenzel, E., & Somoza, V. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200500010 · Cited by 677 · see citing works
Redox modifications of protein-thiols: emerging roles in cell signaling.
Biswas, S., Chida, A., & Rahman, I. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.10.044 · Cited by 631 · see citing works
Resveratrol as an anticancer nutrient: molecular basis, open questions and promises
Signorelli, P., & Ghidoni, R. (2005) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2005.01.017 · Cited by 493 · see citing works
Joe, A. K., Liu, H., Suzui, M., Vural, M. E., Xiao, D., & Weinstein, I. B. (2002) · PubMed · Cited by 455 · see citing works
Kode, A., Rajendrasozhan, S., Caito, S., Yang, S.-R., Megson, I. L., & Rahman, I. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00361.2007 · Cited by 447 · see citing works
Figueira, T. R., de Barros, M. H., Camargo, A. A., Castilho, R. F., Ferreira, J. C. B., Kowaltowski, A. J., Sluse, F. E., de Souza-Pinto, N. C., & Vercesi, A. E. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4729 · Cited by 417 · see citing works
Resveratrol: Its Biologic Targets and Functional Activity
Pervaiz, S., & Holme, A. L. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2412 · Cited by 411 · see citing works
Resveratrol as a Chemopreventive Agent: A Promising Molecule for Fighting Cancer
Delmas, D., Lançon, A., Colin, D., Jannin, B., & Latruffe, N. (2006) · Current Drug Targets · doi:10.2174/138945006776359331 · Cited by 396 · see citing works
Glutathione in liver diseases and hepatotoxicity
Yuan, L., & Kaplowitz, N. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.08.003 · Cited by 359 · see citing works
Resveratrol: One molecule, many targets
Pirola, L., & Fröjdö, S. (2008) · IUBMB Life · doi:10.1002/iub.47 · Cited by 349 · see citing works
Hepatic fibrosis: molecular mechanisms and drug targets
Lotersztajn, S., Julien, B., Teixeira-Clerc, F., Grenard, P., & Mallat, A. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095906 · Cited by 325 · see citing works
Resveratrol commonly displays hormesis: Occurrence and biomedical significance
Calabrese, E. J., Mattson, M. P., & Calabrese, V. (2010) · Human & Experimental Toxicology · doi:10.1177/0960327110383625 · Cited by 276 · see citing works
Mitochondrial fission/fusion dynamics and apoptosis
Sheridan, C., & Martin, S. J. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.08.005 · Cited by 237 · see citing works
Autophagy in health and disease. 5. Mitophagy as a way of life
Gottlieb, R. A., & Carreira, R. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00097.2010 · Cited by 228 · see citing works
The effects of superoxide dismutase on H2O2 formation
Liochev, S. I., & Fridovich, I. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.02.015 · Cited by 202 · see citing works
Juan, M. E., Wenzel, U., Daniel, H., & Planas, J. M. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf800175a · Cited by 199 · see citing works
Autophagy in Health and Disease
Gözüaçık, D. (2013) · Elsevier eBooks · doi:10.1016/c2010-0-66523-0 · Cited by 194 · see citing works
Lipid peroxidation: control of cell proliferation, cell differentiation and cell death
Barrera, G., Pizzimenti, S., & Dianzani, U. (2007) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2007.09.012 · Cited by 159 · see citing works
Robb, E. L., Page, M. M., Wiens, B. E., & Stuart, J. A. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.12.138 · Cited by 147 · see citing works
Lorge, E., Hayashi, M., Albertini, S., et al. (2008) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2008.06.003 · Cited by 135 · see citing works
Nutritional Antioxidants and Adaptive Cell Responses: An Update
Speciale, A., Chirafisi, J., Saija, A., & Cimino, F. (2011) · Current Molecular Medicine · doi:10.2174/156652411798062395 · Cited by 132 · see citing works
Hormesis, cell death and aging
Martins, I., Galluzzi, L., & Kroemer, G. (2011) · Aging · doi:10.18632/aging.100380 · Cited by 128 · see citing works
Research Strategies in the Study of the Pro-Oxidant Nature of Polyphenol Nutraceuticals
Babich, H., Schuck, A. G., Weisburg, J. H., & Zuckerbraun, H. L. (2011) · Journal of Toxicology · doi:10.1155/2011/467305 · Cited by 128 · see citing works
Oxidative Stress, Thiols, and Redox Profiles
Harris, C., & Hansen, J. M. (2012) · Methods in molecular biology · doi:10.1007/978-1-61779-867-2_21 · Cited by 118 · see citing works
Dietary resveratrol administration increases MnSOD expression and activity in mouse brain
Robb, E. L., Winkelmolen, L., Visanji, N. P., Brotchie, J. M., & Stuart, J. A. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.05.028 · Cited by 116 · see citing works
Pervaiz, S., & Clement, M. (2002) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.6274 · Cited by 113 · see citing works
Hassan-Khabbar, S., Cottart, C., Wendum, D., Vibert, F., Clot, J., Savouret, J., Conti, M., & Nivet‐Antoine, V. (2008) · Liver Transplantation · doi:10.1002/lt.21405 · Cited by 91 · see citing works
Establishment of a continuous cell line from fibrotic schistosomal granulomas in mice livers
Borojević, R., Monteiro, Á. N. A., Vinhas, S. A., Domont, G. B., Mourão, P. A. S., Emonard, H., Grimaldi, G., & Grimaud, J.-A. (1985) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02623469 · Cited by 89 · see citing works
Ahmad, K. A., Clement, M., Hanif, I. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2414 · Cited by 88 · see citing works
Iciek, M., Chwatko, G., Lorenc‐Koci, E., Bald, E., & Włodek, L. B. (2004) · Acta Biochimica Polonica · doi:10.18388/abp.2004_3564 · Cited by 87 · see citing works
Gong, C., Tao, G., Yang, L., Liu, J., He, H., & Zhuang, Z. (2011) · Molecular Biology Reports · doi:10.1007/s11033-011-1287-z · Cited by 84 · see citing works
Hydrogen Peroxide Induces G2 Cell Cycle Arrest and Inhibits Cell Proliferation in Osteoblasts
Li, M., Zhao, L., Liu, J., Liu, A., Zeng, W., Luo, S.-Q., & Bai, X. (2009) · The Anatomical Record · doi:10.1002/ar.20925 · Cited by 76 · see citing works
Chua, P., Yip, G. W. C., & Bay, B. (2009) · Experimental Biology and Medicine · doi:10.3181/0903-rm-98 · Cited by 73 · see citing works
Berardi, V., Ricci, F., Castelli, M., Galati, G., & Risuleo, G. (2009) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-28-96 · Cited by 72 · see citing works
Hormetic response of resveratrol against cardioprotection.
Juhász, B., Mukherjee, S., & Das, D. K. (2010) · PubMed · Cited by 64 · see citing works
in vitro小核試験における細胞毒性の正しい評価のための異なる方法の比較 I.理論的側面
Lorge, E., Hayashi, M., Albertini, S., et al. (2008) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · Cited by 63 · see citing works
Rüweler, M., Gülden, M., Maser, E., et al. (2009) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2009.09.003 · Cited by 53 · see citing works
EXPERIMENTAL & CLINICAL CARDIOLOGY
Haider, S., & Fernández‐Ortíz, A. (2014) · Cited by 44 · see citing works
In vitro induction of the fat-storing phenotype in a liver connective tissue cell line-GRX
Borojević, R., Guaragna, R. M. V. D. C., Margis, R., et al. (1990) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02623827 · Cited by 43 · see citing works
Relationship between oxidative stress levels and activation state on a hepatic stellate cell line
Guimarães, E. L. M., Franceschi, M. F. S., Grivicich, I., Dal‐Pizzol, F., Moreira, J. C. F., Guaragna, R. M. V. D. C., Borojević, R., Margis, R., & Guma, F. T. C. R. (2006) · Liver International · doi:10.1111/j.1478-3231.2006.01245.x · Cited by 41 · see citing works
Self-citationde Oliveira, M. R., Pasquali, M. A. D. B., Silvestrin, R. B., Souza, T. M. E., & Moreira, J. C. F. (2007) · Brain Research · doi:10.1016/j.brainres.2007.07.008 · Cited by 41 · see citing works
Self-citationResveratrol inhibits cell growth by inducing cell cycle arrest in activated hepatic stellate cells
de Souza, I. C. C., Martins, L. A. M., Coelho, B. P., Grivicich, I., Guaragna, R. M. V. D. C., Gottfried, C., Borojević, R., & Guma, F. T. C. R. (2008) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-008-9781-x · Cited by 41 · see citing works
Self-citationGuma, F. T. C. R., Mello, T. G., Mermelstein, C., et al. (2001) · Biochemistry and Cell Biology · doi:10.1139/o01-027 · Cited by 40 · see citing works
Self-citationEstimation of Free Thiols and Disulfide Bonds Using Ellman’s ReagentPreprint
Simpson, R. J. (2008) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot4699 · Cited by 39 · see citing works
Martucci, R. B., Ziulkoski, A. L., Fortuna, V., et al. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20073 · Cited by 34 · see citing works
Kawada, N., Kuroki, T., Kobayashi, K., Inoue, M., & Kaneda, K. (1996) · Digestive Diseases and Sciences · doi:10.1007/bf02091547 · Cited by 33 · see citing works
Capsaicin induces de-differentiation of activated hepatic stellate cell
Bitencourt, S., de Mesquita, F. C., Caberlon, E., Haute, G. V., Basso, B. D. S., Ferreira, G. A., & de Oliveira, J. R. (2012) · Biochemistry and Cell Biology · doi:10.1139/o2012-026 · Cited by 32 · see citing works
Olas, B., Wachowicz, B., Bald, E., et al. (2004) · PubMed · Cited by 28 · see citing works
Actions of redox-active compound resveratrol under hydrogen peroxide insult in C6 astroglial cells
Quincozes‐Santos, A., Andreazza, A. C., Gonçalves, C., & Gottfried, C. (2009) · Toxicology in Vitro · doi:10.1016/j.tiv.2009.11.016 · Cited by 23 · see citing works
Self-citationSuperoxide anion is involved in the early apoptosis mediated by Gleditsia sinensis fruit extract
Teo, I., Tang, J. C. O., Chui, C. H., et al. (2004) · International Journal of Molecular Medicine · doi:10.3892/ijmm.13.6.909 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Potential Adverse Effects of Resveratrol: A Literature Review
Shaito, A., Posadino, A. M., Younes, N., Hasan, H., Halabi, S., Alhababi, D., Al-Mohannadi, A., Abdel-Rahman, W. M., Eid, A. H., Nasrallah, G. K., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062084 · Cited by 716 · see citing works
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
- Authors
- Martins, L. A. M., Coelho, B. P., Behr, G., Pettenuzzo, L. F., Souza, I. C. C., Moreira, J. C. F., Borojevic, R., Gottfried, C., & Guma, F. C. R.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- ORCID
- Venue
- Cell Biochemistry and Biophysics
- Published
- 2013-06-21
- Volume
- 68
- Issue
- 2
- Pages
- 247-257
- ISSN
- 1085-9195 (ISSN-L)
- 1559-0283
- OpenAlex
- W1987927672
- Cited by
- 82
- References
- 72
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 12 · 2021: 8 · 2020: 13 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- resveratrol, pro-oxidant activity, hepatic stellate cells, cytotoxicity, oxidative stress, reactive oxygen species, superoxide dismutase, lipid peroxidation, cell viability, cell proliferation, cell cycle arrest, dose-dependent effects, time-dependent resistance
- MeSH terms
- Resveratrol, Animals, Anti-Inflammatory Agents, Non-Steroidal, Catalase, Cell Line, Cell Survival, Stilbenes, Superoxide Dismutase, Time Factors, Lipid Peroxidation, Reactive Oxygen Species, Oxidative Stress, Mice, Hepatic Stellate Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review