Pummelo Protects Doxorubicin-Induced Cardiac Cell Death by Reducing Oxidative Stress, Modifying Glutathione Transferase Expression, and Preventing Cellular Senescence
Open accessAbstract
Citrus flavonoids have been shown to reduce cardiovascular disease (CVD) risks prominently due to their antioxidant effects. Here we investigated the protective effect of pummelo (Citrus maxima, CM) fruit juice in rat cardiac H9c2 cells against doxorubicin (DOX-) induced cytotoxicity. Four antioxidant compositions (ascorbic acid, hesperidin, naringin, and gallic acid) were determined by HPLC. CM significantly increased cardiac cell survival from DOX toxicity as evaluated by MTT assay. Reduction of cellular oxidative stress was monitored by the formation of DCF fluorescent product and total glutathione (GSH) levels. The changes in glutathione-S-transferase (GST) activity and expression were determined by enzyme activity assay and Western blot analysis, respectively. Influence of CM on senescence-associated β-galactosidase activity (SA-β-gal) was also determined. The mechanisms of cytoprotection involved reduction of intracellular oxidative stress, maintaining GSH availability, and enhanced GST enzyme activity and expression. DOX-induced cellular senescence was also attenuated by long-term CM treatment. Thus, CM fruit juice can be promoted as functional fruit to protect cells from oxidative cell death, enhance the phase II GSTP enzyme activity, and decrease senescence phenotype population induced by cardiotoxic agent such as DOX.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Hesperidin attenuates senescence-related oxidative damage in cardiomyocytes, both independently and in combination with other molecules, through induction of Nrf2 and GST expression.
“Its properties impact positively on cardiomyocytes as it attenuates senescence-related oxidative damage, both independently and in combination with other molecules, through the induction of Nrf2 and of GST expression [247,296,297].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [296]
GA can reduce senescence markers in rat embryonic fibroblast cells, delay thymus involution in old mice, and protect cardiac cells from oxidative damage and senescence, enhancing GST expression.
“Indeed, it has been shown that GA can reduce senescence markers in rat embryonic fibroblast cells, delay thymus involution in old mice, and protect cardiac cells from oxidative damage and senescence, enhancing GST expression [296,323,353].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [296]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477 · see citing works
Griffith, O. W. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90139-6 · Cited by 4,628 · see citing works
Doxorubicin-Induced Cardiomyopathy
Singal, P. K., & Iliskovic, N. (1998) · New England Journal of Medicine · doi:10.1056/nejm199809243391307 · Cited by 1,848 · see citing works
Benavente-García, O., & Castillo, J. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf8006568 · Cited by 1,158 · see citing works
Glutathione-S-transferase family of enzymes
Strange, R. C., Spiteri, M. A., Ramachandran, S., & Fryer, A. A. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00206-8 · Cited by 833 · see citing works
Doxorubicin-Induced Cardiomyopathy
Takemura, G., & Fujiwara, H. (2007) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2006.10.002 · Cited by 828 · see citing works
Doxorubicin Induces Apoptosis in Normal and Tumor Cells via Distinctly Different Mechanisms
Wang, S., Konorev, E. A., Kotamraju, S., Joseph, J., Kalivendi, S. V., & Kalyanaraman, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400944200 · Cited by 610 · see citing works
Adriamycin-induced oxidative mitochondrial cardiotoxicity
Berthiaume, J. M., & Wallace, K. B. (2006) · Cell Biology and Toxicology · doi:10.1007/s10565-006-0140-y · Cited by 411 · see citing works
Cardiomyocyte death in doxorubicin-induced cardiotoxicity
Zhang, Y.-W., Shi, J., Li, Y., & Wei, L. (2009) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-009-0051-8 · Cited by 387 · see citing works
Scartezzini, P., Antognoni, F., Raggi, M. A., Poli, F., & Sabbioni, C. (2005) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2005.08.065 · Cited by 239 · see citing works
Kalivendi, S. V., Kotamraju, S., Zhao, H., Joseph, J., & Kalyanaraman, B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106829200 · Cited by 225 · see citing works
Maejima, Y., Adachi, S., Ito, H., Hirao, K., & Isobe, M. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00358.x · Cited by 224 · see citing works
Intake of fruit and vegetables and the risk of ischemic stroke in a cohort of Danish men and women
Johnsen, S. P., Overvad, K., Stripp, C., Tjønneland, A. M., Husted, S., & Sørensen, H. T. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/78.1.57 · Cited by 188 · see citing works
Spallarossa, P., Altieri, P., Aloi, C., Garibaldi, S., Barisione, C., Ghigliotti, G., Fugazza, G., Barsotti, A., & Brunelli, C. (2009) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00068.2009 · Cited by 154 · see citing works
Gururaj Joshi, A., Hardas, S. S., Rukhsana Sultana, A., Clair, D. K. S., Vore, M. E., & Butterfield, D. A. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21158 · Cited by 134 · see citing works
Wattanapitayakul, S. K., Chularojmontri, L., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S., & Bauer, J. A. (2005) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2005.pto960112.x · Cited by 123 · see citing works
Self-citationThe Aging Cardiomyocyte: A Mini-Review
Bernhard, D., & Laufer, G. (2008) · Gerontology · doi:10.1159/000113503 · Cited by 110 · see citing works
Knight, T. R., Choudhuri, S., & Klaassen, C. D. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm233 · Cited by 105 · see citing works
Glutathione S-transferase overexpression protects against anthracycline-induced H9C2 cell death.
L'ecuyer, T., Allebban, Z., Thomas, R. L., & Heide, R. V. (2004) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00778.2003 · Cited by 90 · see citing works
Citrus fruit intake and stomach cancer risk: a quantitative systematic review
Bae, J., Lee, E. J., & Guyatt, G. H. (2008) · Gastric Cancer · doi:10.1007/s10120-007-0447-2 · Cited by 83 · see citing works
Isolation and identification of phenolic compounds in Citrus sinensis
Swatsitang, P., Tucker, G. A., Robards, K., et al. (2000) · Analytica Chimica Acta · doi:10.1016/s0003-2670(00)00937-5 · Cited by 77 · see citing works
The Role of Curcuma longa Against Doxorubicin (Adriamycin)-Induced Toxicity in Rats
Mohamad, R. H., El-Bastawesy, A. M., Zekry, Z. K., Al-Mehdar, H. A., Al-said, M. G. A. M., Aly, S. S., Sharawy, S. M., & El-Merzabani, M. M. (2009) · Journal of Medicinal Food · doi:10.1089/jmf.2007.0715 · Cited by 65 · see citing works
Yu, S.-T., Chen, T.-M., Chern, J., et al. (2009) · Anti-Cancer Drugs · doi:10.1097/cad.0b013e32832a2cd4 · Cited by 61 · see citing works
Aptekmann, N. P., & Cesar, T. B. (2010) · Maturitas · doi:10.1016/j.maturitas.2010.07.009 · Cited by 61 · see citing works
Shi, R., Huang, C.-C., Aronstam, R. S., et al. (2009) · BMC Pharmacology · doi:10.1186/1471-2210-9-7 · Cited by 57 · see citing works
Stuetz, W., Prapamontol, T., Hongsibsong, S., et al. (2010) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf904608h · Cited by 54 · see citing works
Grape Seed Proanthocyanidins Ameliorate Doxorubicin-Induced Cardiotoxicity
Li, J., Liu, H., Ramachandran, S., Waypa, G. B., Yin, J., Li, C., Han, M., Huang, H., Sharp, W. W., Hoek, T. L. V., et al. (2010) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x10008068 · Cited by 48 · see citing works
Barberis, A., Bazzu, G., Calia, G., et al. (2010) · Analytical Chemistry · doi:10.1021/ac100303p · Cited by 41 · see citing works
Ding, L. S., Luo, X., Tang, F., et al. (2007) · Journal of Chromatography B · doi:10.1016/j.jchromb.2007.07.018 · Cited by 38 · see citing works
Ramos, D. L., Gaspar, J., Pingarilho, M., et al. (2011) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2011.04.013 · Cited by 34 · see citing works
Snyder, S. M., Reber, J. D., Freeman, B. L., Orgad, K., Eggett, D. L., & Parker, T. L. (2011) · Nutrition Research · doi:10.1016/j.nutres.2011.06.006 · Cited by 31 · see citing works
Pichaiyongvongdeeand, S., & Haruenkit, R. (2009) · Witthayasan Kasetsat Witthayasat · Cited by 21 · see citing works
Seitz (2009) · International Journal of Oncology · doi:10.3892/ijo_00000523 · Cited by 20 · see citing works
Rolland, D. C. M., Raharijaona, M., Barbarat, A., et al. (2010) · PubMed · Cited by 20 · see citing works
Chularojmontri, L., Ihara, Y., Muroi, E., et al. (2009) · PubMed · Cited by 6 · see citing works
Self-citationRadical scavenging activity of orange and tangerine varieties cultivated in Brazil
Duzzioni, A. G., Franco, A. G., & de Sylos, C. M. (2009) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637480902769575 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
- Chularojmontri, L., Gerdprasert, O., & Wattanapitayakul, S. K.
- Affiliations
- Thammasat University (TH)
- Srinakharinwirot University (TH)
- Corresponding author
- Wattanapitayakul, S. K.
- Venue
- Evidence-Based Complementary and Alternative Medicine
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-9
- ISSN
- 1741-427X (ISSN-L)
- 1741-4288
- PMC
- PMC3564430
- OpenAlex
- W2082518364
- Cited by
- 21
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2015: 2 · 2014: 2 · 2013: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Evidence-based Complementary and Alternative Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Srinakharinwirot University (329/2552, RDG5120068)
- Thailand Research Fund (329/2552, RDG5120068)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Bioactive Compounds in Plants
- Keywords
- pomelo, doxorubicin cardiotoxicity, oxidative stress, glutathione S-transferase, cellular senescence, cardiac cell death, citrus flavonoids, hesperidin, naringin, gallic acid, vitamin C, glutathione, cardioprotection
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
