Abstract
Doxorubicin (DOX) is a potent and broad-spectrum drug widely used in the treatment of cancer. However, the toxicity and side effects of DOX on various organs limit its clinical use. Approaches using natural antioxidants with these drugs have the potential to alleviate negative side effects. The aim of this study was to investigate the potential protective effect of tannic acid, a polyphenolic compound found naturally in plants, against DOX-induced spleen toxicity. Expression levels of Alox5, Inos, IL-6, Tnf-α, Casp-3, Bax, SOD, GST, CAT and GPx genes were determined using cDNAs obtained from spleen tissues of rats treated with DOX, tannic acid and both. In addition, SOD, CAT, GPx and GST enzyme activities, and GSH and MDA levels were measured in tissues. In the spleen tissues, DOX caused a decrease in the level of GSH and an increase in the level of MDA. In addition, it was determined that DOX had a suppressive effect on CAT, GST, SOD and GPx mRNA levels and its enzyme activities, which are antioxidant system components. The mRNA expression levels of proinflammatory cytokine markers, apoptotic genes, and some factors involved in cell metabolism showed a change compared to the control after DOX application. However, as a result of tannic acid treatment with DOX, these changes approached the values of the control group. The findings showed that tannic acid had a protective effect on the changes in the oxidative stress and inflammation system in the rat spleen as a result of the application of tannic acid together with DOX.
Similar content being viewed by others
Data availability
Data will be made available on request.
References
Abo-Salem OM (2012) The protective effect of aminoguanidine on doxorubicin-induced nephropathy in rats. J Biochem Mol Toxicol 26:1–9. https://doi.org/10.1002/jbt.20422
Aebi H (1984) [13] Catalase in vitro. Methods Enzymol:121–126. https://doi.org/10.1016/S0076-6879(84)05016-3
Ahmed F, Urooj A, Karim A (2013) Protective effects of Ficus racemosa stem bark against doxorubucin-induced renal and testicular toxicity. Pharmacogn Mag 9:130. https://doi.org/10.4103/0973-1296.111265
Ahmed RG (2005) The Physiological and Biochemical Effects of Diabetes on the Balance between Oxidative Stress and Antioxidant Defense System. Med J Islamic World Acad Sci 15:31–42
Akomolafe SF, Akinyemi AJ, Anadozie SO (2014) Phenolic Acids (Gallic and Tannic Acids) Modulate Antioxidant Status and Cisplatin Induced Nephrotoxicity in Rats. Int Sch Res Notices 2014:1–8. https://doi.org/10.1155/2014/984709
Aktan F (2004) iNOS-mediated nitric oxide production and its regulation. Life Sci 75:639–653. https://doi.org/10.1016/j.lfs.2003.10.042
Amara-Mokrane YA, Lehucher-Michel MP, Balansard G, Duménil G, Botta A (1996) Protective effects of α-hederin, chlorophyllin and ascorbic acid towards the induction of micronuclei by doxorubicin in cultured human lymphocytes. Mutagen 11:161–167. https://doi.org/10.1093/mutage/11.2.161
Andreadou, I., Sigala, F., Iliodromitis, E.K., Papaefthimiou, M., Sigalas, C., Aligiannis, N., Savvari, P., Gorgoulis, V., Papalabros, E., , Dimitrios Th Kremastinos, 2007. Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress. J Mol Cell Cardiol 42, 549–558. doi:https://doi.org/10.1016/j.yjmcc.2006.11.016
Apel K, Hirt H (2004) Reactive oxygen species: Metabolism, Oxidative Stress, and Signal Transduction. Annu Rev Plant Biol 55:373–399. https://doi.org/10.1146/annurev.arplant.55.031903.141701
Aung T, Qu Z, Kortschak R, Adelson D (2017) Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action. Int J Mol Sci 18:656. https://doi.org/10.3390/ijms18030656
Barabási A-L, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5:101–113. https://doi.org/10.1038/nrg1272
Bartsch H, Nair J (2006) Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair. Langenbecks Arch Surg 391:499–510. https://doi.org/10.1007/s00423-006-0073-1
Behroozaghdam M, Hashemi M, Javadi G, Mahdian R, Soleimani M (2015) Expression of bax and bcl2 Genes in MDMA-induced Hepatotoxicity on Rat Liver Using Quantitative Real-Time PCR Method through Triggering Programmed Cell Death. Iran Red Crescent Med J 17. https://doi.org/10.5812/ircmj.24609
Beutler E (1984) Red Cell Metabolism: A Manual of Biochemical Methods, 3rd edn. Grune & Stratton, Orlando FL
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/0003-2697(76)90527-3
Ceylan H, Budak H, Kocpinar EF, Baltaci NG, Erdogan O (2019) Examining the link between dose-dependent dietary iron intake and Alzheimer’s disease through oxidative stress in the rat cortex. J Trace Elem Med Biol 56:198–206. https://doi.org/10.1016/j.jtemb.2019.09.002
Demaria M, O’Leary MN, Chang J, Shao L, Liu S, Alimirah F, Koenig K, Le C, Mitin N, Deal AM, Alston S, Academia EC, Kilmarx S, Valdovinos A, Wang B, de Bruin A, Kennedy BK, Melov S, Zhou D et al (2017) Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discov 7:165–176. https://doi.org/10.1158/2159-8290.CD-16-0241
Dong B, Liu C, Xue R, Wang Y, Sun Y, Liang Z, Fan W, Jiang J, Zhao J, Su Q, Dai G, Dong Y, Huang H (2018) Fisetin inhibits cardiac hypertrophy by suppressing oxidative stress. J Nutr Biochem 62:221–229. https://doi.org/10.1016/j.jnutbio.2018.08.010
Dudka J, Jodynis-Liebert J, Korobowicz E, Burdan F, Korobowicz A, Szumilo J, Tokarska E, Klepacz R, Murias M (2005) Activity of NADPH-Cytochrome P-450 Reductase of the Human Heart, Liver and Lungs in the Presence of (-)-Epigallocatechin Gallate, Quercetin and Resveratrol: An in vitro Study. Basic Clin Pharmacol Toxicol 97:74–79. https://doi.org/10.1111/j.1742-7843.2005.pto_98.x
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6
El-Moselhy MA, El-Sheikh AAK (2014) Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity. Biomed Pharmacother 68:101–110. https://doi.org/10.1016/j.biopha.2013.09.001
Francis F, Vanhaelen N, Haubruge E (2005) Glutathione S-transferases in the adaptation to plant secondary metabolites in theMyzus persicae aphid. Arch Insect Biochem Physiol 58:166–174. https://doi.org/10.1002/arch.20049
Gao L, Chen Q, Gong T, Liu J, Li C (2019) Recent advancement of imidazolate framework (ZIF-8) based nanoformulations for synergistic tumor therapy. Nanoscale 11:21030–21045. https://doi.org/10.1039/C9NR06558J
Ghigo A, Li M, Hirsch E (2016) New signal transduction paradigms in anthracycline-induced cardiotoxicity. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1863:1916–1925. https://doi.org/10.1016/j.bbamcr.2016.01.021
Gülçin İ, Huyut Z, Elmastaş M, Aboul-Enein HY (2010) Radical scavenging and antioxidant activity of tannic acid. Arabian Journal of Chemistry 3:43–53. https://doi.org/10.1016/j.arabjc.2009.12.008
Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-Transferases. J Biol Chem 249:7130–7139. https://doi.org/10.1016/S0021-9258(19)42083-8
Jadapalli JK, Wright GW, Kain V, Sherwani MA, Sonkar R, Yusuf N, Halade GV (2018) Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium. Am J Physiol Heart Circ Physiol 315:H1091–H1100. https://doi.org/10.1152/ajpheart.00290.2018
Jones ML, Mark PJ, Keelan JA, Barden A, Mas E, Mori TA, Waddell BJ (2013) Maternal dietary omega-3 fatty acid intake increases resolvin and protectin levels in the rat placenta. J Lipid Res 54:2247–2254. https://doi.org/10.1194/jlr.M039842
Kann MG (2007) Protein interactions and disease: computational approaches to uncover the etiology of diseases. Brief Bioinform 8:333–346. https://doi.org/10.1093/bib/bbm031
Li F, Luo P, Liu H (2018) A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides. Mar Drugs 16:106. https://doi.org/10.3390/md16040106
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757–772. https://doi.org/10.2147/CIA.S158513
Livak KJ, Schmittgen TD (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
Lu J, Guo X, Yan M, Yuan X, Chen S, Wang Y, Zhu J, Huang S, Shen H, Li H, Xue Q, Fang Q, Ni J, Gan L, Zhao H, Lu H, Chen G (2021) P2X4R Contributes to Central Disinhibition Via TNF-α/TNFR1/GABAaR Pathway in Post-stroke Pain Rats. J Pain 22:968–980. https://doi.org/10.1016/j.jpain.2021.02.013
Ludke A, Sharma AK, Bagchi AK, Singal PK (2012) Subcellular basis of vitamin C protection against doxorubicin-induced changes in rat cardiomyocytes. Mol Cell Biochem 360:215–224. https://doi.org/10.1007/s11010-011-1059-z
Maqsood S, Benjakul S (2011) Retardation of haemoglobin-mediated lipid oxidation of Asian sea bass muscle by tannic acid during iced storage. Food Chem 124:1056–1062. https://doi.org/10.1016/j.foodchem.2010.07.077
Nie F, Liang Y, Jiang B, Li X, Xun H, He W, Lau HT, Ma X (2016) Apoptotic effect of tannic acid on fatty acid synthase over-expressed human breast cancer cells. Tumor Biology 37:2137–2143. https://doi.org/10.1007/s13277-015-4020-z
Pacher P, Liaudet L, Bai P, Mabley JG, Kaminski PM, Virág L, Deb A, Szabó E, Ungvári Z, Wolin MS, Groves JT, Szabó C (2003) Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction. Circulation 107:896–904. https://doi.org/10.1161/01.CIR.0000048192.52098.DD
Ren Y, Li X, Han B, Zhao N, Mu M, Wang C, Du Y, Wang Y, Tong A, Liu Y, Zhou L, You C, Guo G (2019) Improved anti-colorectal carcinomatosis effect of tannic acid co-loaded with oxaliplatin in nanoparticles encapsulated in thermosensitive hydrogel. Eur J Pharm Sci 128:279–289. https://doi.org/10.1016/j.ejps.2018.12.007
Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B, Peyvandi AA (2014) Protein-protein interaction networks (PPI) and complex diseases. Gastroenterol Hepatol Bed Bench 7:17–31. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017556/pdf/GHFBB-7-017.pdf. Accessed 02 Jul 2023
Sartoretto SM, Santos FF, Costa BP, Ceravolo GS, Santos-Eichler R, Carvalho MHC, Fortes ZB, Akamine EH (2019) Involvement of inducible nitric oxide synthase and estrogen receptor ESR2 (ERβ) in the vascular dysfunction in female type 1 diabetic rats. Life Sci 216:279–286. https://doi.org/10.1016/j.lfs.2018.11.030
Sarveswaran S, Chakraborty D, Chitale D, Sears R, Ghosh J (2015) Inhibition of 5-Lipoxygenase Selectively Triggers Disruption of c-Myc Signaling in Prostate Cancer Cells. J Biol Chem 290:4994–5006. https://doi.org/10.1074/jbc.M114.599035
Sengupta A, Manna K, Datta S, Das U, Biswas S, Chakrabarti N, Dey S (2017) Herbicide exposure induces apoptosis, inflammation, immune modulation and suppression of cell survival mechanism in murine model. RSC Adv 7:13957–13970. https://doi.org/10.1039/C6RA27883C
Soyocak A, Kurt H, Cosan DT, Saydam F, Calis IU, Kolac UK, Koroglu ZO, Degirmenci I, Mutlu FS, Gunes HV (2019) Tannic acid exhibits anti-inflammatory effects on formalin-induced paw edema model of inflammation in rats. Hum Exp Toxicol 38:1296–1301. https://doi.org/10.1177/0960327119864154
Suleyman H, Cadirci E, Albayrak A, Polat B, Halici Z, Koc F, Hacimuftuoglu A, Bayir Y (2009) Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats. Chem Biol Interact 180:318–324. https://doi.org/10.1016/j.cbi.2009.03.002
Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500. https://doi.org/10.1093/clinchem/34.3.497
Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, Altman RB (2011) Doxorubicin pathways. Pharmacogenet Genomics 21:440–446. https://doi.org/10.1097/FPC.0b013e32833ffb56
Tsang W, Ho FYF, Fung K, Kong S, Kwok T (2005) p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer 114:331–336. https://doi.org/10.1002/ijc.20818
van Cutsem E, Arends J (2005) The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs 9:S51–S63. https://doi.org/10.1016/j.ejon.2005.09.007
Xu C, Shu W-Q, Qiu Z-Q, Chen J-A, Zhao Q, Cao J (2007) Protective effects of green tea polyphenols against subacute hepatotoxicity induced by microcystin-LR in mice. Environ Toxicol Pharmacol 24:140–148. https://doi.org/10.1016/j.etap.2007.04.004
Yesilkent EN, Ceylan H (2022) Investigation of the multi-targeted protection potential of tannic acid against doxorubicin-induced kidney damage in rats. Chem Biol Interact 365:110111. https://doi.org/10.1016/j.cbi.2022.110111
Zhang J, Cui L, Han X, Zhang Y, Zhang X, Chu X, Zhang F, Zhang Y, Chu L (2017a) Protective effects of tannic acid on acute doxorubicin-induced cardiotoxicity: Involvement of suppression in oxidative stress, inflammation, and apoptosis. Biomed Pharmacother 93:1253–1260. https://doi.org/10.1016/j.biopha.2017.07.051
Zhang J, Song Q, Han X, Zhang Y, Zhang Y, Zhang X, Chu X, Zhang F, Chu L (2017b) Multi-targeted protection of acetaminophen-induced hepatotoxicity in mice by tannic acid. Int Immunopharmacol 47:95–105. https://doi.org/10.1016/j.intimp.2017.03.027
Zhou G-X, Ding X-L, Wu S-B, Zhang H-F, Cao WEI, Qu L-S, Zhang H (2015) Inhibition of 5-lipoxygenase triggers apoptosis in pancreatic cancer cells. Oncol Rep 33:661–668. https://doi.org/10.3892/or.2014.3650
Zhu J, Ye Q, Xu S, Chang Y, Liu X, Ma Y, Zhu Y, Hua S (2019) Shengmai injection alleviates H2O2-induced oxidative stress through activation of AKT and inhibition of ERK pathways in neonatal rat cardiomyocytes. J Ethnopharmacol 239:111677. https://doi.org/10.1016/j.jep.2019.01.001
Acknowledgements
Authors would like to acknowledge the funding from Atatürk University by Scientific Research Project Coordination Unit (Grant Number: FYL-2021-9395).
Funding
This study was funded by Ataturk University Scientific Research Project Coordination Unit (Grant Number: FYL-2021-9395).
Author information
Authors and Affiliations
Contributions
M.K. and H.C. designed the experiments. M.K. and D.K performed the experiments and wrote the paper. M.K. and H.C. analyzed the data. M.K. was responsible for funding acquisition and project management. The authors declare that all data were generated in-house and that no paper mill was used.
Corresponding author
Ethics declarations
Ethical approval
All experimental procedures were performed in accordance with a protocol approved by Atatürk University Local Ethics Council for Animal Experiments (Protocol No: 2021/3–65).
Competing interests
The authors declare that there are no conflicts of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Kizir, D., Karaman, M. & Ceylan, H. Tannic acid may ameliorate doxorubicin-induced changes in oxidative stress parameters in rat spleen. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3605–3613 (2023). https://doi.org/10.1007/s00210-023-02563-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-023-02563-w