Epigallocatechin gallate and coenzyme Q10 attenuate cisplatin‐induced hepatotoxicity in rats via targeting mitochondrial stress and apoptosis
Abstract
Despite the extensive use of cisplatin (CP) as a chemotherapeutic agent, its clinical use is often restricted by undesirable side effects, such as toxicity to normal tissues. The aim of this study was to probe the effect of a combinatorial treatment of low multiple doses of antioxidants on CP‐induced toxicity and the mitochondrial apoptotic pathway in hepatocytes. Animals received a single toxic dose of CP (7.5 mg/kg body weight) with or without combined multiple doses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight, respectively). CP‐treated animals showed altered biochemical parameters, denoting hepatotoxicity, which was markedly improved by the multidose treatment with EGCG + CoQ10. The increased levels of oxidants found in the cytosolic and mitochondrial fractions isolated from the liver of CP‐administered rats were significantly attenuated by the combinatorial doses of antioxidants. EGCG + CoQ10 ameliorated the CP‐induced compromised antioxidant defenses, oxidative modification of macromolecules, decreased activities of respiratory chain enzymes, altered membrane depolarization, and swelling of liver mitochondria. Furthermore, EGCG + CoQ10 treatment inhibited CP‐induced apoptosis by suppressing the activation and mitochondrial accumulation of proapoptotic proteins and preventing the inhibition of antiapoptotic protein expression, cytochrome c efflux, caspase‐3 activation, and DNA fragmentation. Histological findings further confirmed the protective effects of EGCG + CoQ10 against CP‐induced cellular injury. Our findings revealed that the combination of EGCG and CoQ10, owing to their individual antioxidant properties, can be an effective remedy, which by maintaining redox hemostasis attenuate the mitochondrial stress‐mediated molecular and cellular processes involved in CP‐induced liver toxicity and cell death.
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CoQ10 inhibits activation of caspase-3 and release of cytochrome c from mitochondria by stabilizing the mitochondrial membrane, suppresses proapoptotic genes caspase-3 and Bax, stimulates antiapoptotic Bcl2, and prevents translocation of nuclear apoptosis-inducing factors.
“This is in line with Sumi et al. (2018) and Fatima et al. (2021) who stated that CoQ10 inhibited the activation of caspase-3 and the release of cytochrome c from mitochondria via stabilizing the mitochondrial membrane, thus preventing the release of apoptotic mediators.”
From Can coenzyme Q10 alleviate the toxic effect of fenofibrate on skeletal muscle? (2023) · cites this paper as Fatima et al. 2021
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
[49] Determination of carbonyl content in oxidatively modified proteins
Levine, R. L., Garland, D. L., Oliver, C. N., Amici, A., Climent, I., Lenz, A.-G., Ahn, B. W., Shaltiel, S., & Stadtman, E. R. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)86141-h · Cited by 5,895 · see citing works
Cisplatin in cancer therapy: Molecular mechanisms of action
Dasari, S., & Bernard Tchounwou, P. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.07.025 · Cited by 5,537 · see citing works
Activation of apoptosis signalling pathways by reactive oxygen species
Redza-Dutordoir, M., & Averill-Bates, D. A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.09.012 · Cited by 3,731 · see citing works
Mitochondria and cell death: outer membrane permeabilization and beyond
Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593 · see citing works
Controlled drug delivery vehicles for cancer treatment and their performance
Senapati, S., Mahanta, A. K., Kumar, S., & Maiti, P. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-017-0004-3 · Cited by 2,167 · see citing works
Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species
He, L., He, T., Farrar, S., Ji, L., Liu, T., & Ma, X. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000485089 · Cited by 2,142 · see citing works
The multiple mechanisms that regulate p53 activity and cell fate
Hafner, A., Bulyk, M. L., Jambhekar, A., & Lahav, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0110-x · Cited by 1,129 · see citing works
Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells
Spinazzi, M., Casarin, A., Pertegato, V., Salviati, L., & Angelini, C. I. (2012) · Nature Protocols · doi:10.1038/nprot.2012.058 · Cited by 989 · see citing works
Determination of Inorganic Nitrate in Serum and Urine by a Kinetic Cadmium-Reduction Method
Cortas, N. K., & Wakid, N. W. (1990) · Clinical Chemistry · doi:10.1093/clinchem/36.8.1440 · Cited by 894 · see citing works
Systems biology of cisplatin resistance: past, present and future
Galluzzi, L., Vitale, I., Michels, J., Brenner, C., Szabadkai, G., Harel-Bellan, A., Castedo, M., & Kroemer, G. (2014) · Cell Death & Disease · doi:10.1038/cddis.2013.428 · Cited by 782 · see citing works
Mitochondrial DNA mutations and human disease
Tuppen, H. A. L., Blakely, E. L., Turnbull, D. M., & Taylor, R. W. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.005 · Cited by 676 · see citing works
Vaseva, A. V., & Moll, U. M. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.10.005 · Cited by 618 · see citing works
Katerji, M., Filippova, M., & Duerksen-Hughes, P. J. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/1279250 · Cited by 435 · see citing works
The mitochondrial permeability transition pore: a mystery solved?
Bernardi, P. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00095 · Cited by 335 · see citing works
Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments
Chu, C., Deng, J., Man, Y., & Qu, Y. (2017) · BioMed Research International · doi:10.1155/2017/5615647 · Cited by 335 · see citing works
Negri, A., Naponelli, V., Rizzi, F., & Bettuzzi, S. (2018) · Nutrients · doi:10.3390/nu10121936 · Cited by 307 · see citing works
Singh, K., Bhori, M., Kasu, Y. A. T., Bhat, G. M., & Marar, T. (2017) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2017.12.013 · Cited by 295 · see citing works
Choi, Y.-M., Kim, H., Shim, W., Anwar, M. A., Kwon, J.-W., Kwon, H., Kim, H. J., Jeong, H., Kim, H. M., Hwang, D., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135083 · Cited by 283 · see citing works
Acute nephrotoxicity of cisplatin: Molecular mechanisms
Peres, L. A. B., & Júnior, A. D. D. C. (2013) · Brazilian Journal of Nephrology · doi:10.5935/0101-2800.20130052 · Cited by 261 · see citing works
Oxidatively induced DNA damage and its repair in cancer
Dizdaroğlu, M. (2014) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2014.11.002 · Cited by 254 · see citing works
Mitochondrial energy generation disorders: genes, mechanisms, and clues to pathology
Frazier, A. E., Thorburn, D. R., & Compton, A. G. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.809194 · Cited by 254 · see citing works
Regulation of DNA fragmentation: the role of caspases and phosphorylation
Kitazumi, I., & Tsukahara, M. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07975.x · Cited by 224 · see citing works
van Gisbergen, M. W., Voets, A. M., Starmans, M. H. W., de Coo, I. F. M., Yadak, R., Hoffmann, R. F., Boutros, P. C., Smeets, H. J. M., Dubois, L. J., & Lambin, P. (2015) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2015.01.001 · Cited by 199 · see citing works
Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels
Mailloux, R. J. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7857251 · Cited by 189 · see citing works
DNA damage response in cisplatin-induced nephrotoxicity
Zhu, S., Pabla, N., Tang, C., He, L., & Dong, Z. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1633-3 · Cited by 183 · see citing works
Coenzyme Q10: The essential nutrient
Saini, R. (2011) · Journal of Pharmacy And Bioallied Sciences · doi:10.4103/0975-7406.84471 · Cited by 182 · see citing works
Mitochondrial Roles and Cytoprotection in Chronic Liver Injury
Esposti, D. D., Hamelin, J., Bosselut, N., Saffroy, R., Sebagh, M., Pommier, A., Martel, C., & Lemoine, A. (2012) · Biochemistry Research International · doi:10.1155/2012/387626 · Cited by 159 · see citing works
Garrido‐Maraver, J., Cordero, M. D., Oropesa-Ávila, M., Fernández-Vega, A., de la Mata, M., Pavón, A. D., de Miguel, M., Calero, C. P., Paz, M. V., Cotán, D., et al. (2014) · Molecular Syndromology · doi:10.1159/000360101 · Cited by 154 · see citing works
Sahu, B. D., Kumar, J. M., & Sistla, R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134139 · Cited by 147 · see citing works
Li, F., Feng, Y. Y., Chen, G., Qin, L., Chun-ling, F., & Chen, L. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.01.032 · Cited by 145 · see citing works
Tangeretin Alleviates Cisplatin-Induced Acute Hepatic Injury in Rats: Targeting MAPKs and Apoptosis
Omar, H. A., Mohamed, W. R., Arab, H. H., & Arafa, E. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151649 · Cited by 143 · see citing works
Jung, T., Höhn, A., & Grune, T. (2014) · Redox Biology · doi:10.1016/j.redox.2013.12.029 · Cited by 134 · see citing works
Is coenzyme Q a key factor in aging?
López‐Lluch, G., Rodríguez‐Aguilera, J. C., Santos‐Ocaña, C., & Navas, P. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.02.003 · Cited by 129 · see citing works
Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit
Kart, A., Çiğremiş, Y., Karaman, M., & Özen, H. (2009) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2009.02.066 · Cited by 122 · see citing works
Mi, X.-J., Hou, J., Wang, Z., Han, Y., Ren, S., Hu, J., Chen, C., & Li, W. (2018) · Scientific Reports · doi:10.1038/s41598-018-34156-6 · Cited by 105 · see citing works
Omar, H. A., Mohamed, W. R., Arafa, E. A., et al. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.09.007 · Cited by 102 · see citing works
Cisplatin hepatotoxicity mediated by mitochondrial stress
Waseem, M., Bhardwaj, M., Tabassum, H., Raisuddin, S., & Parvez, S. (2015) · Drug and Chemical Toxicology · doi:10.3109/01480545.2014.992437 · Cited by 77 · see citing works
Caro, A. A., Adlong, L. W., Crocker, S. J., Gardner, M. W., Luikart, E. F., & Gron, L. U. (2012) · Toxicology Letters · doi:10.1016/j.toxlet.2012.08.017 · Cited by 69 · see citing works
Ameliorative Effects of Taurine Against Methimazole-Induced Cytotoxicity in Isolated Rat Hepatocytes
Heidari, R. (2012) · Scientia Pharmaceutica · doi:10.3797/scipharm.1205-16 · Cited by 63 · see citing works
Han, J., Goldstein, L. A., Hou, W., Gastman, B., & Rabinowich, H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.081042 · Cited by 61 · see citing works
Fatima, S., Al‐Mohaimeed, N., Al‐Shaikh, Y., et al. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.05.023 · Cited by 55 · see citing works
Self-citationHyperin protects against cisplatin-induced liver injury in mice
Niu, C., Ma, M., Han, X., et al. (2017) · Acta Cirúrgica Brasileira · doi:10.1590/s0102-865020170080000005 · Cited by 51 · see citing works
Ahmad, S., Hussain, A., Hussain, A., Abdullah, I., Ali, M. S., Froeyen, M., & Mirza, M. U. (2019) · Antioxidants · doi:10.3390/antiox8060185 · Cited by 46 · see citing works
Time course of cisplatin-induced nephrotoxicity and hepatotoxicity
Pezeshki, Z., Khosravi, A., Nekuei, M., et al. (2017) · Journal of Nephropathology · doi:10.15171/jnp.2017.28 · Cited by 44 · see citing works
Farooq, N., Priyamvada, S., Anbazhagan, A. N., Salim, S., Khan, F., & Yusufi, A. N. K. (2006) · British Journal Of Nutrition · doi:10.1017/bjn20061942 · Cited by 35 · see citing works
Afsar, T., Razak, S., Almajwal, A. M., et al. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1824-y · Cited by 26 · see citing works
Huang, T., Chiu, Y., Chan, Y.-L., Wang, H., Li, T., Liu, C.-Y., Yang, C., Lee, T.-Y., You, J., Hsu, K., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4348 · Cited by 23 · see citing works
Fatima, S., Al‐Mohaimeed, N., Arjumand, S., et al. (2014) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.21671 · Cited by 22 · see citing works
Self-citationCosta, A. R., Machado, N., Rego, A., Sousa, M. J., Côrte‐Real, M., & Chaves, S. R. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.10.006 · Cited by 14 · see citing works
Barquero, C. E. B., Vázquez-Zapién, G. J., & Mata-Miranda, M. M. (2019) · Nefrología · doi:10.1016/j.nefro.2018.11.012 · Cited by 10 · see citing works
Corbin, M., & Bossaer, J. B. (2017) · Hospital Pharmacy · doi:10.1177/0018578717715356 · Cited by 5 · see citing works
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Can coenzyme Q10 alleviate the toxic effect of fenofibrate on skeletal muscle?
El-Bassouny, D. R., Mansour, A. A., Ellakkany, A. S., Ayuob, N. N., & AbdElfattah, A. A. (2023) · Histochemistry and Cell Biology · doi:10.1007/s00418-023-02205-5
- Authors
- Fatima, S., Suhail, N., Alrashed, M., Wasi, S., Aljaser, F. S., AlSubki, R. A., Alsharidah, A. S., & Banu, N.
- Affiliations
- King Saud University (SA)
- Northern Border University (SA)
- Imam Abdulrahman Bin Faisal University (SA)
- Qassim University (SA)
- Corresponding author
- Fatima, Sabiha
- ORCID
- Venue
- Journal of Biochemical and Molecular Toxicology
- Publisher
- Wiley
- Published
- 2021-01-04
- Volume
- 35
- Issue
- 4
- Pages
- e22701-e22701
- ISSN
- 0887-2082 (ISSN-L)
- 1095-6670
- 1099-0461
- OpenAlex
- W3120796915
- Cited by
- 25
- References
- 52
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 2 · 2023: 5 · 2022: 5
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biochemical and Molecular Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Chemotherapy-induced organ toxicity mitigation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Keywords
- cisplatin, hepatotoxicity, epigallocatechin gallate, coenzyme Q10, mitochondrial stress, apoptosis, oxidative stress, antioxidants, caspase-3, mitochondrial depolarization, hepatoprotection, redox homeostasis, chemotherapy-induced liver injury
- MeSH terms
- Animals, Catechin, Cisplatin, Liver, Male, Mitochondria, Liver, Ubiquinone, Rats, Wistar, Apoptosis, Oxidative Stress, Hepatocytes, Rats, Chemical and Drug Induced Liver Injury
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